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

Know your brain: Reticular formation

Where is the reticular formation?

The reticular formation is found in the brainstem, at the center of an area of the brainstem known as the tegmentum. The tegmentum is a heterogeneous section of neural tissue that extends vertically through the brainstem, making up the portion of the brainstem that sits between the ventricles and surface structures like the basal pons and the pyramids of the medulla. As the reticular formation is found at the core of the tegmentum, it too runs along the length of the brainstem.

What is the reticular formation and what does it do?

The reticular formation is a very diverse structure that contains various nuclei along with numerous ascending and descending tracts. The fibers that traverse the reticular formation give the region a net-like appearance, which is where it gets its name (reticular means net-like). Due to the heterogeneity of the structure, as well as to the fact that there are not clear boundaries between the nuclei within the reticular formation, it was originally thought to lack organization. However, it is now clear that the reticular formation is highly organized, just very intricate and complex. Of the numerous cell groups and tracts found throughout the reticular formation or connected to reticular formation neurons, some worth noting are nuclei involved in neurotransmitter production, nuclei associated with the cranial nerves, descending tracts involved in modulating sensory and motor functions, and ascending tracts integral to arousal and consciousness.

The reticular formation is home to several groups of cells that produce neurotransmitters; these neuronal populations have extensive connections throughout the central nervous system and are involved in the regulation of activity throughout the brain. One of the largest dopamine-producing areas in the brain, the ventral tegmental area, is located in the reticular formation, as is the locus ceruleus, which is the largest collection of noradrenergic neurons in the brain. The primary sites of serotonin release in the brain, the raphe nuclei, are found near the midline of the brainstem in the reticular formation. And, some of the largest sites of acetylcholine production in the brain, the pedunculopontine nucleus and laterodorsal tegmental nucleus, are found in the midbrain reticular formation. Neurotransmitters are produced in all of these areas and sent throughout the central nervous system to modulate sensory perception, motor activity, and behavioral responses.

Reticular formation neurons also form circuits with the motor nuclei of the cranial nerves; these nuclei contain neurons that are responsible for motor movements in the face and head, as well as motor movements related to autonomic functions of the visceral organs. Reticular formation circuitry helps to coordinate the activity of neurons in these cranial nerve nuclei, and thus is involved in the regulation of simple motor behaviors. For example, reticular formation neurons in the medulla facilitate motor activity associated with the vagus nerve. This activity involves functions of the gastrointestinal system (e.g. swallowing, vomiting), respiratory functions (e.g. coughing, sneezing, breathing rhythm), and cardiovascular functions (e.g. maintenance of blood pressure). Reticular neurons in the medulla and pons also contribute to orofacial motor responses by coordinating activity in motor nuclei for the trigeminal, facial, and hypoglossal nerves. This activity, for example, allows for movements of the jaw, lips, and tongue that lead to the movements required for chewing and eating. Reticular formation neurons are also important for facilitating the operation of muscles that allow for emotional facial expressions, like laughing or crying, as well as for coordinating eye movements.

The reticular formation contains long ascending (i.e. traveling to the brain) and descending (i.e. traveling from the brain to the body) tracts. The descending projections are primarily involved with the modulation of sensory and motor pathways. For example, projections extend from the raphe nuclei down to the dorsal horn of the spinal cord and can act to inhibit pain sensations. This is thought to be a major component of descending pain control systems that allow us to suppress pain in certain situations (e.g. during a traumatic event). Other descending projections from the reticular formation are involved in the control of posture and movement. These fibers are mainly found in the reticulospinal tract, which extends from the reticular formation to help maintain posture, facilitate stereotyped movements like stepping, and modulate muscle tone to either aid or inhibit movement.

The reticular formation may be best known for its role in promoting arousal and consciousness. This function is mediated by the reticular activating system (RAS), also known as the ascending arousal system. The reticular activating system contains circuits that originate in several areas of the brainstem, including the midbrain reticular formation, and ascend to the cerebral cortex and thalamus. These pathways are predominantly associated with the neurotransmitters acetylcholine and norepinephrine, both of which are thought to play important roles in regulating arousal and wakefulness. The cholinergic neurons originate in the pedunculopontine nucleus and laterodorsal tegmental nuclues, while the noradrenergic neurons originate in the locus coeruleus. The fibers that arise from these locations combine with other pathways that ascend to the cerebral cortex and thalamus to promote wakefulness, vigilance, and overall arousal. These pathways from the reticular formation must be functional for normal attentional abilities and sleep-wake cycles to be preserved. Lesions to major pathways of the reticular activating system can thus impair consciousness, and severe damage can cause coma or a persistent vegetative state.

Kandel ER, Schwartz JH, Jessell TM 2000. Principles of Neural Science, 5th ed. McGraw-Hill, New York.

2-Minute Neuroscience: Pain and the Anterolateral System

In this video, I discuss pain and the anterolateral system. I describe the three main pathways of the anterolateral system: the spinothalamic, spinoreticular, and spinomesencephalic tracts. I follow the route pain information takes along each of these tracts, from nociceptors to the somatosensory cortex, reticular formation, or periaqeuductal grey (depending on the tract).

The powerful influence of placebos on the brain

The term placebo effect describes an improvement in the condition of a patient after being given a placebo--an inert substance (e.g. sugar pill) the patient expects may hold some benefit for him. The placebo effect has long been recognized as an unavoidable aspect of medical treatment. Physicians before the 1950s often took advantage of this knowledge by giving patients treatments like bread pills or injections of water with the understanding that patients had a tendency to feel better when they were given something--even if it was inactive--than when they were given nothing at all. In the years following World War II, it became recognized that the placebo effect is more than just a medical curiosity--it is an extremely potent influence on patient psychology and physiology. With this realization came the determination that a condition where participants are given a placebo is a necessary component of an experiment designed to assess the effectiveness of a drug; for, if just the act of receiving treatment makes patients feel better, then that improvement must be subtracted from the overall strength of a drug's action to determine the true efficacy of the substance. This awareness led to the use of placebo conditions in clinical trials of pharmaceutical drugs being commonplace, and to the modern conception of the placebo effect as an important component of drug effects.

While many of us are aware of the use of placebos to test the effectiveness of drugs, we may be less likely to realize that some fraction of the benefit of any drug we take is likely due to the placebo effect. Because we expect the medications we take to help us feel better, they generally do to some extent; this influence is added to the efficacy of the mechanistic action of the drug to produce its overall effect. The magnitude of the contribution of the placebo effect can range from minor to the majority of the drug effect, depending on the medicine in question. Thus, the placebo effect in medicine is something that influences many of us on a daily basis, and all of us at some point or another.

The potency of the placebo effect

The magnitude of the placebo effect is often under-appreciated. Although placebos have no active ingredients, they have been shown to influence both psychology and physiology, and in some cases the effects of a placebo have been found to be stronger than the effects of the medication being compared against it. Placebos can improve quality of life, mitigate the burden of a disability, and--amazingly--have even been associated with decreased mortality. For example, in studies of patients with congestive heart failure, those who adhered to taking placebos regularly were 50% less likely to die than those who were in the placebo group but didn't adhere to taking their "medication." Those who faithfully took placebos were also less likely to experience cardiovascular events like stroke or heart attack.

The effects of placebos on a number of physiological systems have now been well documented. Placebos have been found to influence the activity of the autonomic nervous system, such as heart rate, gastrointestinal activity, and respiration. Placebos can elicit changes in hormone levels across various functional systems; effects have ranged from reducing stress hormone levels based on expectation alone to decreasing levels of appetite-stimulating hormones by convincing participants they had just eaten a very calorie-rich food (even though they hadn't). Researchers have even found that placebos can affect the activity of the immune system. In one study, investigators elicited immunosuppression as a placebo-induced response, and in another study it was found that watching advertisements for the antihistamine drug Claritin led to the drug being more effective than it was in participants who didn't receive any pro-drug messages.

Despite all of the experiments that have documented placebo effects, there is still a great deal to be learned about which neurobiological systems are necessary for creating the placebo effect. It may be that the neurobiology of the placebo effect is different depending on the type of stimulus or the expectancies involved. In other words, it is not clear if there is a group of brain regions and/or pathways that are activated whenever the placebo effect occurs--regardless of the circumstances--or if there are different regions activated depending on the context of the placebo administration. Recent research has used neuroimaging to attempt to unravel the mechanism underlying the placebo effect and, while the effect is complex and still poorly understood, these studies have provided some insight into which areas of the nervous system may be important to mediating it.

Neuroimaging of the placebo effect

Much of the experimental evidence regarding the placebo effect comes from studies of the impact of placebos on pain. This is due in part to the early recognition that the experience of pain is amenable to manipulation by the use of placebos. Pain is also useful to study because it is a ubiquitous problem that has relevance for clinical practice; additionally, we have a fairly good understanding of the components of the nervous system that are involved in pain sensations.

There are several brain regions that receive direct innervation from pathways that carry nociceptive (i.e. pain-related) information from the body to the brain. These include: the thalamus, through which pain signals must pass as they travel to the cortex; the somatosensory cortex, which is the cortical area where sensory signals from the body are initially processed; the insula, which is thought to be involved in mediating the intensity and emotional response to pain; and the anterior cingulate cortex, which is also believed to be involved in emotional responses to pain. Treatment with a placebo has been found to decrease activity in all of the above areas, and several studies have found that larger placebo responses were associated with a greater reduction of activity in these regions.

In addition to affecting these pain "centers" in the brain, placebos have also been found to activate pathways that travel down from the brainstem to the spinal cord to inhibit pain responses. The best known of these pathways runs from an area in the midbrain called the periaqueductal grey, down to the spinal cord. Activation of the periaqueductal grey can be initiated by a variety of cortical areas, and leads to increases in levels of natural painkillers known as endogenous opioids, which act to suppress pain. Endogenous opioids are part of an adaptive mechanism that allows us to tolerate pain, presumably to ensure we can extricate ourselves from an acutely dangerous situation before we become preoccupied with pain sensations.

Placebos can activate these descending pain modulatory pathways involving the periaqueductal grey to cause increases in levels of endogenous opioids. Some studies have found that increased activity in the periaqueductal grey is associated with the degree of placebo analgesia experienced. Additionally, administering a drug called naloxone that blocks the receptors where endogenous opioids normally exert their effect causes a decrease in placebo-induced analgesia. Thus, it seems that activity in the periaqueductal grey is an important component of placebo-induced pain relief. 

Placebos also affect activity in higher brain regions like the prefrontal cortex, amygdala, and striatum. Changes in activity in these areas may cause alterations in levels of endogenous opioids and/or may involve changes in affective and anticipatory states, which may influence the perception of pain. Connections between the prefrontal cortex and periaqueductal grey seem to be important for placebo analgesia, as placebos can cause increased activity in areas of the prefrontal cortex; this activity is associated with increased periaqueductal grey stimulation and endogenous opioid release. Placebo treatments also elevate levels of endogenous opioids in the amygdala, and reduce activity there. The role most commonly attributed to the amygdala involves the detection of threats in the environment and the generation of anxiety about those threats, and thus reduced activity in the amygdala may mitigate the anxiety-producing impact of pain. Placebo treatments also cause increases in both dopaminergic and endogenous opioid activity in the striatum. Dopamine activity in the striatum is generally associated with learning, motivation, and emotion; it has been hypothesized that the striatum may be involved in encoding information about the rewarding nature of pain relief and the aversive aspects of pain itself, and thus in the learning and behavior associated with pain avoidance.

Although the placebo effect has been explored most comprehensively in regards to pain, it is not confined to mitigating painful sensations; placebos have been found to affect experiences ranging from emotion to movement in Parkinson's disease. In many cases, the same systems discussed above in the context of pain are thought to be involved. For example, being given a placebo anti-anxiety medication led to decreased activity in the amygdala in response to a series of negative images; participants also rated the images as less unpleasant after taking the placebo. Studies in Parkinson's disease patients have found that taking a placebo that is expected to facilitate movement can cause increased dopamine levels in the striatum, which is associated with improvements in mobility.

Thus, it seems that the brain areas mentioned above may not be specific to the type of placebo effect explored, and may be part of some underlying neural circuitry that mediates the placebo effect in general. However, it is also likely true that we are just scratching the surface with the identification of these common areas. The full neural circuitry of the placebo effect is probably more complex than the collection of regions outlined above, and presumably includes a more intricate neurochemical basis than just endogenous opioids and dopamine. For example, recent research has identified roles for hormones like cholecystokinin and oxytocin in the placebo response as well.

Additionally, it is unclear if brain regions like the prefrontal cortex, which are activated in different types of placebo responses, are activated to serve the same purpose in each context. For example, in a pain context the prefrontal cortex may be involved in activating the periaqueductal grey; in a situation where someone is given a placebo anti-anxiety drug, however, the prefrontal cortex may be involved with regulation of areas like the amygdala. Thus, it is uncertain if this shared neural circuitry is actually working in the same manner in different placebo situations.

Research will therefore continue into the phenomenon of the placebo effect, for more than just the sake of curiosity. For, if we can learn more about the placebo effect and how it is mediated by the brain, we can use that knowledge to better predict which patients might be likely to experience a large placebo effect, and which would not. An ability to predict placebo response in patients could be immensely valuable, and could turn the placebo effect from a quirky aspect of medical care to something that can be directly manipulated in order to improve the effectiveness of treatment. And, while we may not return to the days of giving bread pills without consent, we may be able to better evaluate the efficacy of medications if we are able to better understand the contribution the placebo effect is having.

Wager, T., & Atlas, L. (2015). The neuroscience of placebo effects: connecting context, learning and health Nature Reviews Neuroscience, 16 (7), 403-418 DOI: 10.1038/nrn3976

2-Minute Neuroscience: The Cochlea

In this video, I discuss the cochlea. I describe the passage of sound waves through the ear, which leads to the depression of the oval window, a structure found in the wall of the cochlea. I cover the three main cavities in the cochlea: the scala vestibuli, scala media, and scala tympani. Then I describe how the movement of fluid in the cochlea causes movement of the basilar membrane, which activates hair cells in the organ of Corti. The hair cells transmit the auditory information to the vestibulocochlear nerve, which carries it to the brain to be processed.

Read more about the cochlea: Know your brain: Cochlea