The neuroscience of traumatic brain injury

The Centers for Disease Control and Prevention estimates that as many as 1.7 million people in the United States experience a traumatic brain injury (TBI) each year, over 15% of which are thought to be sports-related. Despite the relatively high prevalence of these injuries, however, it seems we are just beginning to appreciate the true extent of the effects they can have on the brain. Awareness of previously unrecognized consequences to TBI and repeated TBI--along with the realization that TBI may occur more frequently than previously believed in high-impact sports like American football--has sparked a great deal of interest in gaining a better understanding of the neurobiological consequences of these injuries.

Types of TBI

TBI can be considered acute, which refers to a recent injury and its short-term effects, or chronic, which describes the accumulated neurobiological effects of repeated TBI. The most common acute TBI is mild TBI, which is also known as a concussion. A concussion doesn't result in any overt pathology (e.g. bleeding, obvious structural damage) in the brain, but can cause a variety of symptoms including dizziness, nausea, headache, impairments in concentration and memory, and even loss of consciousness. The discernibility of symptoms can range from very apparent to subtle enough that they are difficult to detect without formal assessment. For some, these symptoms will disappear within minutes to hours after the injury. However, about 40-80% of people who experience a concussion will develop post-concussion syndrome, which involves prolonged symptoms that last for days or weeks. At least 10% may develop persistent post-concussive syndrome, which entails symptoms that persist for more than 3 months and can continue for longer than a year.

Of course acute TBI can also be much more severe than what is seen in a typical concussion, and can result in contusions (bruises) and/or lacerations of brain tissue as well as potential intracranial bleeding (i.e. bleeding within the skull). Acute TBI of this severity is known as catastrophic brain injury, and may result in death. The most common cause of death in these cases is subdural hematoma, which is a pooling of blood between the dura mater and brain. Such accumulation can increase intracranial pressure to dangerous levels, which can cause damage to (and death of) brain tissue.

The effects of repeated TBI, as may occur in someone who plays a contact sport like American football professionally, can lead to accumulative damage to the brain referred to as chronic traumatic encephalopathy (CTE). This syndrome has long been recognized as a hazard of a career in boxing, causing it to initially be referred to as "punch-drunk syndrome" before it was given the more formal appellation of dementia pugilistica in the 1930s. The disorder has some similarities to dementia, and is associated with cognitive decline, tremors and other movement problems, as well as difficulties with speech that make speech sound slurred (hence the reference to drunkenness in the original descriptor of the syndrome). The overt symptoms of CTE often do not appear until long after the repeated head trauma (e.g. after a boxer has already retired), frequently emerging in midlife, but about 1/3 of CTE cases get progressively worse over time.

Pathophysiology of TBIs

Damage to the brain in TBI can be classified as either focal or diffuse. Focal damage usually occurs after direct impact to a specific part of the head/brain that results in damage that is observable with the naked eye. Focal injuries thus tend to be more severe and involve damage like contusions, lacerations, and hemorrhages. Diffuse injuries, on the other hand, are present in both severe and more mild forms of TBI and are not generally visible without the use of advanced neuroimaging techniques. Diffuse injuries are created when brain tissue is stretched and torn due to the rapid acceleration and deceleration of the head that can be caused by sudden impacts. In this article, I will focus primarily on diffuse injuries as they are the type of injury whose effects can accumulate over time with repeated trauma--even if the injuries themselves are relatively mild in terms of symptoms produced. Thus, while focal injuries are recognized as cause for immediate concern, diffuse injuries can, for example, affect athletes over the course of a career without debilitating symptoms only to lead to premature cognitive decline once the career has ended.

Diffuse axonal injury

Diffuse axonal injury (DAI) is a typical diffuse injury seen in TBI. It involves the physical tearing of axons, the structures that convey electrical signals along neurons to allow neurons to communicate with one another. If the axonal tearing is severe enough, it can initiate a cascade of events that starts with the disruption of the transport of important cellular components (e.g. proteins, organelles) to and from the cell body of the neuron. These materials destined for transport along the axon then collect in clumps within the axon, creating swellings that further disrupt the integrity of the cell until the axon begins to break apart in those areas where the swellings have occurred. This is followed by Wallerian degeneration, a process that describes the full degradation of a section of axon that has been separated from the cell body. Depending on the severity of the injury, DAI can be associated with effects ranging from loss of consciousness to coma. The extent of DAI also is correlated with the severity of postconcussive syndrome symptoms. However, it has been suggested that axonal degeneration is not confined to the period of time immediately following TBI, and may continue for years after the injury

Neurochemical effects

As the disruption of the integrity of axons due to DAI is occurring, there are also widespread changes in neurochemistry that develop, precipitated at least in part by the degeneration of axons. As axons deteriorate, the flow of ions across the neuronal membrane is dysregulated, leading to the excessive release of neurotransmitters like the excitatory neurotransmitter glutamate. The increased release of glutamate causes extensive neuronal excitation; the brain responds by using large amounts of energy to attempt (unsucessfully) to contain this exaggerated neural activity. However, there is not enough glucose to fully meet this energy need, and the brain resorts to a method to generate short-term energy that leads to the accumulation of the compound lactate. Lactate build-up can cause additional neuronal dysfunction, and might make neurons more susceptible to damage should another injury occur.

When glutamate binds to its receptors on neurons, it causes calcium ions to enter the cell. Due to the high levels of glutamate present after TBI, calcium influx into neurons becomes excessive. This can lead to the accretion of calcium within mitochondria, and the subsequent disruption of mitochondrial energy production. In severe cases, intracellular calcium build-up can prompt neurons to initiate apoptotic processes (i.e. neurons commit "cell suicide" due to the negative metabolic consequences of intracellular calcium accumulation). 

Neurofibrillary tangles and amyloid beta plaques

Neurofibrillary tangles and the aggregation of amyloid beta proteins into insoluble clusters called amyloid or senile plaques are both signs of neurodegenerative diseases and hallmarks of Alzheimer's disease. They are also both seen in the brains of individuals who have experienced repeated TBI. It is unclear exactly what role tangles and plaques play in neurodegeneration, and many believe they are part of a protective mechanism instead of promoters of the spread of disease. Regardless, their appearance after TBI causes the brain of someone who has experienced repeated TBI to resemble that of someone who is suffering from neurodegenerative disease.

Neurofibrillary tangles are aggregates of a protein called tau, which is normally involved in the stabilization of components of the cell cytoskeleton called microtubules. During neurodegenerative disease, tau proteins undergo a change called hyperphosphorylation, which disrupts tau's ability to bind to microtubules. Hyperphosphorylated tau then accumulates into the indissoluble tangles in the cytoplasm of neurons. Whether neurofibrillary tangles contribute to the progression of neurodegeneration or are part of a cellular response to stress and insult is unclear. Either way, they are a characteristic sign of brain trauma and neurodegeneration; in Alzheimer's disease the number of tangles has been found to be correlated with the severity of the dementia. And the tangles seen in the brains of those with CTE are similar in structure and chemical makeup to the tangles seen in patients with Alzheimer's disease.

Another hallmark characteristic of Alzheimer's disease is the development of clusters of amyloid beta protein known as amyloid plaques. The non-pathological function of amyloid beta is not very clear, but it is found in the extracellular space surrounding neurons even in healthy brains. Unlike neurofibrillary tangles, amyloid plaques form outside of and around neurons. Similar to neurofibrillary tangles, amyloid plaques are also seen in the brains of individuals with CTE. As is the case with tangles, we aren't sure if the formation of amyloid plaques contributes to the progression of neurodegeneration or represents a failed attempt to mitigate it. Studies have found, however, that the accumulation of amyloid beta and its precursor, amyloid precursor protein, occurs quickly after a TBI (within hours) and the degree of accumulation is correlated with the severity of the injury

Dangerous impact

Thus, when a TBI occurs there are substantial effects on the brain, some of which resemble the same types of neurobiological changes we see in our most devastating neurodegenerative diseases. A better understanding of TBI and its consequences has made the potential effects of repeated head injuries an important topic of sports-related discussions, as it is becoming recognized that popular sports like American football (which are often played by teenagers and adolescents) may pose a risk to the health of their participants. Studies of professional football players, for example, have provided ominous results; in one large study that included the brains of 91 professional football players donated for post-mortem analysis, 87 had evidence of CTE

Concerns also abound for other sports that involve frequent head impacts. Boxing and mixed martial arts are obvious culprits. The available data on the risks inherent to boxing are extensive; the literature on mixed martial arts is more limited, likely due to its relatively recent increase in popularity. However, one can assume that (at least on the professional level) there is some overlap in the degree of risk involved in all combat sports due to the frequent head impacts involved, and the results of studies that have focused on combat sports have generally been concerning. For example, one study found that 87% of former boxers examined displayed evidence of brain dysfunction as indicated by a CAT scan, electroencephalogram, or neuropsychological testing. Another study of neuroimaging results from 100 boxers and mixed martial artists found 76% of them had brain abnormalities consistent with TBI, and the severity of these abnormalities was correlated with the number of fights they had in their career. This should come as no surprise when we consider the results of one study of the force of impact of a punch from a professional heavyweight boxer (former champion Frank Bruno): it was found to be equivalent to the force generated by a 13-pound wooden mallet swung at a speed of 20 miles per hour.

The risk of head injuries, and thus TBI, isn't just confined to the sports that easily come to mind when we think of frequent head impacts, however. For example, the risk in sports like basketball and soccer is also relatively high, and some risk is present in athletic activities ranging from baseball to cheerleading. With all of this information in mind, it is easy to understand why there has been a focus in organizations like the National Football League on new rules designed to keep players from targeting the heads of others, and why head injuries in children's sports have become a national topic of conversation. As we learn more about the neurobiological consequences of TBI, it is likely concern about the potential harm of these injuries will continue to increase instead of abate. However, one can be hopeful that, as our knowledge of TBI also continues to increase, our ability to treat and manage the after-effects of such injuries will improve so we may one day be able to mitigate the long-term consequences of TBI.

Blennow, K., Hardy, J., & Zetterberg, H. (2012). The Neuropathology and Neurobiology of Traumatic Brain Injury Neuron, 76 (5), 886-899 DOI: 10.1016/j.neuron.2012.11.021

2-Minute Neuroscience: Effects of Cocaine on the Brain

In this video, I discuss the effects of cocaine on the brain. I describe cocaine's primary mechanism of action, which involves inhibition of the reuptake of monoamine neurotransmitters like dopamine, norepinephrine, and serotonin. I also discuss the mesocorticolimbic dopamine pathway, which connects the ventral tegmental area with the nucleus accumbens and is activated when someone uses cocaine.

2-Minute Neuroscience: Blood-Brain Barrier

In this video, I discuss the blood-brain barrier, a complex that surrounds most of the blood vessels in the brain and protects the brain from potentially dangerous substances that might be circulating in the blood stream. I discuss the tight junctions of endothelial cells as one of the main structural components of the blood-brain barrier, as well as describe the contribution of astrocytic end-feet to the formation and maintenance of the blood-brain barrier. Finally, I discuss the circumventricular organs as structures in the brain that lack a blood-brain barrier.

Know your brain: Blood-brain barrier

Where is the blood-brain barrier?

The blood-brain barrier surrounds most of the blood vessels in the brain. It is a structure that is formed primarily due to the establishment of tight junctions between endothelial cells (i.e. cells that line the walls of blood vessels). There are also several other cells and proteins contributing to the blood-brain barrier complex; for example, processes called astrocytic end-feet extend from astrocytes to surround blood vessels and provide support to the endothelial cells of the blood-brain barrier.

What is the blood-brain barrier and what does it do?

The blood-brain barrier acts as an additional boundary between the circulating blood and the extracellular space of the brain. The barrier is highly selective, meaning it only allows certain substances to cross from the bloodstream into the brain. This functions to protect the brain from toxins, pathogens, and even circulating neurotransmitters (e.g. glutamate) that can be potentially damaging to neurons if their levels get too high. Only water, certain gases (e.g. oxygen), and lipid-soluble substances can easily diffuse across the barrier (other necessary substances like glucose can be actively transported across the blood-brain barrier with some effort).

It is thought that the central component of the functional anatomy of the blood-brain barrier involves tight junctions formed between endothelial cells, the cells that make up the interior surface of the blood vessels in the brain. In other blood vessels throughout the body, there are spaces between these endothelial cells; small blood-borne substances can pass through such spaces and into surrounding tissues. The endothelial cells that make up the blood-brain barrier, however, are fused tightly together, which restricts passive diffusion across the blood vessel lining.

Projections from astrocytes also extend to the walls of the blood vessels that are part of the blood-brain barrier and often completely surround those vessels. These projections, called astrocytic end-feet, appear to play critical roles in the formation of the blood-brain barrier. For example, they are thought to be involved with signaling that prompts endothelial cells to form the tight junctions necessary to create the blood-brain barrier. They also seem to have multiple functions involving the maintenance of the blood-brain barrier and possibly the transient opening of the barrier to allow important substances to cross in special circumstances.

While most blood vessels in the brain are ensconced in the blood-brain barrier, there are some regions that lack a blood-brain barrier, allowing substances to pass from the blood to the brain and vice versa more freely. For example, the circumventricular organs are a group of structures lacking a blood-brain barrier that are centered around the ventricles of the brain. It is thought blood vessels in the circumventricular organs are more permeable for a reason; for instance, the posterior pituitary gland needs to release hormones directly into the bloodstream and the subfornical organ is involved in cardiovascular regulation, which requires access to the circulatory system to monitor levels of hormones in the blood.

Although the blood-brain barrier is an important layer of protection between the peripheral blood circulation and the brain, in certain situations it can be problematic that access to the brain is so restrictive. For example, in the rare instance where there is an infection of the brain, the blood-brain barrier makes delivery of antimicrobial agents to the brain very difficult; it also impedes the passage of antibodies from the body to the brain. While in these cases the blood-brain barrier may be an obstacle to treatment, however, in general it provides an essential buffer between the circulating blood of the body and the brain.

Ballabh P, Braun A, & Nedergaard M (2004). The blood-brain barrier: an overview: structure, regulation, and clinical implications. Neurobiology of disease, 16 (1), 1-13 PMID: 15207256

2-Minute Neuroscience: Myelin

In this video, I discuss myelin, an insulatory layer that covers the axons of many neurons in the nervous system. I describe myelin's role in promoting efficient neuronal signaling, and I discuss its structure, which consists of stretches of myelin called internodes surrounding intermittent gaps in myelin called nodes of Ranvier. I also discuss the cells that form myelin: Schwann cells in the peripheral nervous system and oligodendrocytes in the central nervous system.

Know your brain: Cingulate cortex

Where is the cingulate cortex?

MRI image showing the cingulate cortex (in red).

MRI image showing the cingulate cortex (in red).

The cingulate cortex is a section of the cerebral cortex found in the medial portion of the cerebral hemispheres. In other words, to get a good view of the cingulate cortex one would have to make a slice through a brain parallel to the midline of the brain, and then look inside; the cingulate cortex is not visible from the surface of the brain. The cingulate cortex consists of the cingulate gyrus--which sits just above the corpus callosum--as well as the adjacent cingulate sulcus. It is sometimes called the limbic cortex and considered part of the limbic lobe, an area of cortex associated with emotional responses. The cingulate cortex is generally divided into anterior and posterior regions (discussed below).

What is the cingulate cortex and what does it do?

Early perspectives on the function of the cingulate cortex suggested the entire structure played an important role in emotion, but it is now thought that there are different functional specializations associated with different parts of the cingulate cortex. The most common method of dividing the structure is to split it into anterior and posterior regions; each is thought to be involved with different tasks.

The anterior cingulate cortex, or ACC, is found at the front of the cingulate cortex and wraps around the head of the corpus callosum. The ACC has connections with a variety of other brain regions, and thus the functions associated with it are diverse. There are, for example, areas of the ACC that are densely interconnected with limbic system structures like the amygdala and hypothalamus. Through these connections, the ACC is thought to be involved with a number of functions related to emotion including the regulation of overall affect, assigning emotions to internal and external stimuli, and making vocalizations associated with the expression of states or desires. The ACC also seems to contribute to the regulation of autonomic and endocrine responses, pain perception, and the selection and initiation of motor movements. Additionally, there are other areas of the ACC that are involved in various aspects of cognition ranging from decision-making to the management of social behavior.

The posterior cingulate cortex, or PCC, lies just behind the anterior cingulate. Although it is believed the PCC has important roles in cognition and affect, there is some debate as to what exactly those roles are. Neuroimaging studies indicate the PCC is active during the recall of autobiographical memories. It is also activated by emotional stimuli, and thus some have suggested it may be recruited for the recall of memories that have an emotional quality (e.g. autobiographical memories). The PCC is also considered part of the default mode network, a group of brain structures that are more active when an individual is not involved in a task that requires externally-focused attention. For example, the PCC is stimulated when someone is daydreaming or recalling memories. Some have asserted that the PCC helps to regulate the balance between internally and externally-focused attention, making it a crucial structure in awareness and attentional focus.

The connections of the cingulate cortex to other brain structures are extensive, and thus the functions of the region are varied and complex. Although there is much still to be learned about the roles of the cingulate cortex, it seems clear it makes important contributions to emotion, various types of cognition, and a number of other physiological functions.

Microbes and the mind: Who's pulling the strings?

There are many examples throughout nature of microorganisms like bacteria, viruses, and parasites influencing the neurobiology and behavior of their hosts. For example, the rabies virus enters the nervous system almost immediately after a bite or scratch and travels to the brain, where it influences neural activity to make aggressive behavior more likely. This, of course, is beneficial for the virus as it increases the probability its infected host will make contact with another susceptible host, in effect improving the likelihood the viral strain will be able to propagate. Another well-known example involves the parasite Toxoplasma gondii, which needs to live in its preferred environment of feline intestines to survive and reproduce. When T. gondii embryos are excreted in the feces of cats, they are consumed by rodents (who are wont to dig through cat feces looking for pieces of undigested food). It is thought that T. gondii then has a mechanism by which it can influence rodent behavior to make rats and mice less afraid of--and perhaps even attracted to--cat urine. The loss of inhibitions regarding the smell of their natural predator's urine causes rodents to be more likely to remain in the vicinity of cats, and thus be consumed by cats. This puts T. gondii right back in its preferred feline intestinal environment, giving the impression that the whole process may have been elegantly orchestrated by the microbial parasite.

Despite the existence of these natural cases of "microbial mind control," it is only very recently that neuroscientists have begun to take the idea seriously that microorganisms may also have an influence on human behavior. With recent advances in research technologies, however, we have learned more about the microorganism populations that inhabit our bodies, and their potential influence on our behavior--although not yet understood--is becoming difficult to dismiss. The gastrointestinal tract has received the most attention in this regard, as it has the most extensive bacterial colonization of any area in the human body. Thus, the gut has become a new target in attempts to understand behaviors ranging from eating, to stress, to disorders like autism.

The gut-brain axis

Researchers have long been aware of a powerful connection between the gut, or gastrointestinal tract, and the brain; it was already clear to 19th and early 20th century scientists like Charles Darwin, William James, and Walter Cannon that strong emotions influenced the functioning of the gastrointestinal system. Near the beginning of the 20th century, it became recognized that the gut is governed by a complex nervous system structure that we now know consists of hundreds of millions of neurons and can operate autonomously (without input from the central nervous system). This neuronal structure, dubbed the enteric nervous system, which can be found in the walls of the gastrointestinal tract from the esophagus to anus, is now considered another branch of the autonomic nervous system (although it is sometimes called our "second brain" due to its complexity and similarities with the brain of the central nervous system). The connections between the brain and the enteric nervous system are extensive; the two can communicate through neuronal, endocrine, and immune system signaling.

The gut microbiota

In addition to having its own nervous system, the gut is also home to up to 100 trillion microorganisms. This number includes over 1,000 different species of microbes, the vast majority of which are bacteria. Together, these microorganisms are thought to outnumber the cells in our body by more than 10 times (which has led writer Michael Pollan to describe us as only 10% human), and they possess about 150 times the number of genes found in our genome. As a whole, gut microorganisms make up the majority of our microbiota, the collection of microorganisms we share our bodies with.

Our resident microorganisms are not just passive roommates, either; they play significant roles in widespread physiological functions. For example, they are likely involved in nutrient absorption, fat storage, and the function and development of a healthy immune system. In fact, it seems like we have what is known as a mutualistic relationship with these microbes, wherein both species (us and the microbes) benefit from our proximity. The microorganisms in our gut are able to dwell in an environment where they can survive and reproduce, and in return they perform a number of functions that promote our own health and viability. 

On the other hand, one could argue that we are simply--as microbiologist Justin Sonnenburg puts it--"an elaborate vessel optimized for the growth and spread of our microbial inhabitants." According to this perspective, it is the microorganisms that are manipulating the evolution and behavior of their host in order to achieve their maximum level of fitness. For example, some researchers believe that, in order to obtain the nutrients they desire, microbes have developed ways of shaping our appetites to make us crave the types of food that will supply those nutrients. But this is just the tip of the iceberg, as the gut microbiota is now being explored as a potential driver of a wide array of human behavior and as an underlying cause in a number of mental disorders.

Gut microbiota and behavior

The range of mechanisms by which gut microbiota may be able to influence human behavior is likely very complex and not yet fully understood, but there are several aspects of gut-brain communication that have been identified as potential drivers of behavior. Some of these are fairly direct. For example, the vagus nerve travels down from the brainstem to innervate the internal organs of the body and provides extensive innervation to the gastrointestinal tract. It represents the most direct connection between the gut and the brain, and studies have found that stimulation of the vagus nerve by microorganisms is associated with changes in behavior, brain function, and neurotransmitter receptor levels in the brain.

Additionally, most of the neurotransmitters found in the brain are also found in the gut at equivalent or greater levels. These neurotransmitters are capable of stimulating the vagus nerve to affect central nervous system function, and the amount of neurotransmitter present in the gut is influenced by the activity of gut microbiota. For example, the vast majority of serotonin in the body is produced in the gut, and its production is regulated by microbial activity there. Additionally, gut microbes are involved in the production of neurotransmitter precursors, which can then cross the blood-brain barrier to affect neurotransmitter synthesis in the brain. Gut microbiota, for example, are involved in the synthesis of tryptophan, the precursor to serotonin. After it is produced, tryptophan can cross the blood-brain barrier to affect serotonin production in the brain.

The influence of gut microbiota on behavior can also be more indirect. For example, gut microbes can affect the activity of the immune system, and alterations in immune system function can impact behavior. A well-known example of the immune system's ability to influence behavior involves sickness behaviors. Sickness behaviors are thought to be an adaptive response to infection; they include things like decreased movement, loss of appetite, increased sleep, and decreased social interaction. A reduction in these otherwise common behaviors is thought to allow for energy conservation and a reduction in the risk of exposure to additional pathogens. One way these behaviors can be initiated is when microorganisms in the gut activate immune system cells, which then send signaling molecules called cytokines to the brain, leading to a modification of one's typical actions.

Clinical relevance of the gut microbiome

At this point, most of the investigative work on the relationship between the gut microbiota and behavior has involved experimental animals like rodents. Although the translation of results from animal models to humans is often problematic, the findings of these studies are intriguing and support the hypothesis that gut microbiota can affect more than just digestion. One approach to investigating this hypothesis has been to raise rodents in a sterile, germ-free environment, and then to compare their behavior with rodents raised in a typical environment. Because the microorganismic colonization of the gastrointestinal tract occurs after birth, rodents raised in germ-free environments never develop the diverse gut microbiota that normal animals do. Interestingly, their behavior is also very different. Germ-free animals display differences in cognition, responses to stress, and neurotransmitter levels, among other things.

The results of these studies are intriguing, but we cannot assume the same phenomena occur in humans until human experiments return similar findings. However, although the majority of the work in this area has been done with rodents, there are some findings with humans that suggest the gut microbiome is also influencing our behavior. One approach to exploring gut microbiota function in humans involves the administration of probiotics, which are microorganisms like certain bacterial strains that are thought to have a beneficial effect when ingested. Some believe particular probiotic formulations can be beneficial to the health of the gastrointestinal tract by replenishing levels of microorganisms that are important to normal gut function.

Because probiotics are capable of modifying the microbiotic composition of the gastrointestinal tract, several experiments have involved the administration of probiotics to humans followed by the monitoring of behavior. For example, in one placebo-controlled clinical trial, patients who received a multi-bacterial probiotic formulation had lower levels of self-reported depression and anxiety symptoms than patients who received placebos. Participants receiving probiotics also had lower urinary levels of the stress hormone cortisol, which supports a growing body of evidence linking the composition of the gut microbiota to stress reactivity and the function of the hypothalamic-pituitary-adrenal (HPA) axis. In another randomized controlled trial, participants who received a probiotic formulation displayed less depressive rumination, fewer aggressive thoughts, and reduced reactivity to sad moods. A 2012 study went a step further and used neuroimaging to explore how probiotics might be influencing brain activity to produce these types of results. The investigators found that participants who were given probiotics displayed less activity in the insula (an area of the brain involved in emotional responses) during an emotional reactivity test.

These findings that repeatedly link the gut microbiota to the central nervous system and behavior have sparked a great deal of interest in the hypothesis that gut microbiota may be involved in a variety of central nervous system-related conditions. One logical area of study, for example, is the role of the gut microbiome in obesity. As mentioned above, it is believed the gut microbiome is capable of manipulating eating behavior in order to obtain the nutrients its microorganisms desire. Interestingly, differences in the makeup of the gut microbiome exist between lean and obese individuals. Additionally, rodents raised in germ-free environments are more resistant to obesity, even when fed a high-fat diet. And, some studies have suggested that probiotic supplementation may aid in weight loss attempts and reduce abdominal fat deposition.

Research, however, has also begun to implicate the gut microbiota in disorders that are less clearly connected with the gastrointestinal tract. For example, due in part to the gastrointestinal symptoms often reported in children with autism spectrum disorders (ASDs), the makeup of the gut microbiome has been hypothesized to play a role in the disorder. Although the studies in this area are still preliminary, some have detected differences in the makeup of the gut microbiota in autistic versus control patients. Additionally, autistic-like behavior has been elicited in rodents after the administration of propionic acid, which is a byproduct of bacterial metabolism in the gut. These types of findings need to be explored further, but they raise intriguing questions about the development of a complex neurological disorder.

The gut microbiota is also being explored as a contributing factor in a number of other disorders ranging from multiple sclerosis to schizophrenia. Still, however, it seems as if we are just scratching the surface when it comes to explorations of the influence of microorganisms on human behavior. It would not be a surprise to many researchers in this area if, over the next couple of decades, we discover that the microorganismic residents of our body are exerting a powerful effect over many of the choices we believe we are making solely with our own free will. And perhaps that would strengthen the argument of the biological determinist--if not only is our behavior controlled by our genetics and our neurobiology, but also by the microscopic residents of our bodies.

Cryan, J., & Dinan, T. (2012). Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour Nature Reviews Neuroscience, 13 (10), 701-712 DOI: 10.1038/nrn3346