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

Know your brain: Default mode network

Where is the default mode network?

The default mode network (sometimes called simply the default network) refers to an interconnected group of brain structures that are hypothesized to be part of a functional system. The default network is a relatively recent concept, and because of this there is not yet a complete consensus on which brain regions should be included in a definition of it. Regardless, some structures that are generally included are the medial prefrontal cortex, posterior cingulate cortex, and the inferior parietal lobule. A few of the other structures that may be considered part of the network are the lateral temporal cortex, hippocampal formation, and the precuneus.

What is the default mode network and what does it do?

The concept of a default mode network was developed after researchers inadvertently noticed surprising levels of brain activity in experimental participants who were supposed to be "at rest"--in other words they were not engaged in a specific mental task, but just resting quietly (often with their eyes closed). Although the idea that the brain is constantly active (even when we aren't engaged in a distinct mental activity) was clearly expressed by Hans Berger in the 1930s, it wasn't until the 1970s that brain researcher David Ingvar began to accumulate data showing that cerebral blood flow (a general measurement of brain activity) during resting states varied according to specific patterns; for example, he observed high levels of activity in the frontal lobes of participants at rest.

As neuroimaging methods became more accurate, data continued to accumulate that suggested activity during resting states followed a certain order; this data was easy to come by because in many neuroimaging studies, asking participants to rest in a quiet state is considered the control condition. In the early 2000s, Raichle, Gusnard, and colleagues published a series of articles that attempted to more specifically define the areas of the brain that were most active during these rest states. It was in one of these publications that they used the term default mode to refer to this resting activity, phraseology which led to the brain areas that exhibited default mode activity being considered part of the default mode network.

Thus, the default mode network is a group of brain regions that seem to show lower levels of activity when we are engaged in a particular task like paying attention, but higher levels of activity when we are awake and not involved in any specific mental exercise. It is during these times that we might be daydreaming, recalling memories, envisioning the future, monitoring the environment, thinking about the intentions of others, and so on--all things that we often do when we find ourselves just "thinking" without any explicit goal of thinking in mind. Additionally, recent research has begun to detect links between activity in the default mode network and mental disorders like depression, anxiety, and schizophrenia. Furthermore, therapies like meditation have received attention for influencing activity in the default mode network, suggesting this may be part of their mechanism for improving well-being.

The concept of a default mode network is not without controversy. There are some who argue that it is difficult to define resting wakefulness as constituting a unique state of activity, as energy consumption during this state is similar to energy consumption during other waking states. Others have asserted that it is unclear what the patterns of activity during these resting states mean, and thus what the functional importance of the connections between the regions in the default mode network really are.

These caveats are worth keeping in mind when you come across research on the default mode network, as--especially due to its relationship with meditation--it is becoming a frequently-used term in popular neuroscience descriptions of brain activity. The idea of a default mode network, however, is not universally accepted; even those who endorse the idea concede there still is a lot of work left to do to figure out the network's exact functions. Regardless, at the very least the concept of a default mode network has sparked interest in understanding what the brain is doing when it is not involved in a specific task, and this line of research may help us to gain a more comprehensive understanding of brain function.

Buckner RL, Andrews-Hanna JR, & Schacter DL (2008). The brain's default network: anatomy, function, and relevance to disease. Annals of the New York Academy of Sciences, 1124, 1-38 PMID: 18400922

2-Minute Neuroscience: The Retina

In this video, I cover the retina. I discuss the five major types of neurons found in the retina: photoreceptor cells (i.e. rods and cones), bipolar cells, ganglion cells, horizontal cells, and amacrine cells. I also briefly describe the fovea, our area of highest visual acuity, and the optic disc, which creates a natural blind spot in our visual field.

Deep brain stimulation in Parkinson's disease: Uncovering the mechanism

Parkinson's disease (PD) belongs to a group of diseases that are referred to as neurodegenerative because they involve the degeneration and death of neurons. In PD a group of structures called the basal ganglia, which play a role in facilitating movement, are predominantly affected. The substantia nigra, one of the basal ganglia nuclei as well as one of the most dopamine-rich areas in the brain, is severely impacted; by the end stages of the disease patients have often lost 50-70% of the dopamine neurons in this region. This excessive loss of dopamine neurons and the accompanying depletion of dopamine levels in the basal ganglia are associated with increasingly debilitating movement-related symptoms, such as rigidity, tremor, bradykinesia (slow movement), and postural impairment.

The most common method of treating PD involves the administration of L-DOPA. L-DOPA is a precursor to dopamine that the brain can use to synthesize more of the neurotransmitter; thus, it works to increase the dopamine levels that are being continuously reduced by the disease. PD, however, is progressive, meaning that neurodegeneration will continue once it has begun. L-DOPA isn't capable of halting neurodegeneration, and eventually the dopamine synthesized from L-DOPA is not enough to replace all that has been lost due to the disorder; with time L-DOPA begins to lose its effectiveness. Especially in the later stages of PD, L-DOPA provides diminishing returns, and the side effects of chronic L-DOPA treatment start to make its continued use more detrimental than beneficial.

Therefore, we continue to seek out treatments for PD that will be more effective in the advanced stages of the disease (while maintaining a manageable side effect profile). In the early 1990s, it was observed in non-human primates that lesions of the subthalamic nucleus (STN) appeared to effectively eradicate Parkinsonian symptoms. Although the reason for this was not fully understood, a hypothesis was formulated based on the understanding that one of the functions of the STN seems to be to inhibit unwanted movements. Normally, this suppression of movement should only occur when a movement is not desired, and thus the interference should be removed with the attempt to initiate movement. In PD, decreased dopamine levels may prevent another structure in the basal ganglia, the globus pallidus, from moderating activity in the STN. This can lead to excessive STN activity, which serves to overly-inhibit movements and may cause the difficulty in making movements that characterizes PD. Based on this rationale and related experimental evidence, the STN was identified as a potential therapeutic target in PD. At that point, though, the only way to reduce activity in the STN was through a surgical procedure that irreversibly destroyed the nucleus.

However, not long after the STN was identified as playing a role in PD symptoms, a new method of influencing activity in the STN (and other brain areas) was developed: deep brain stimulation (DBS). This method was tested in patients with PD for the first time in the mid-1990s. The results were encouraging, as in some cases symptoms improved drastically and the patients were able to reduce their dose of L-DOPA and related drugs significantly. An example of the marked improvements that can occur after DBS is initiated can be seen in the video to the right. Since the first experimental DBS procedures, the method has been used with thousands of patients, making it an established therapeutic approach for the treatment of advanced PD.

Deep brain stimulation procedure

DBS involves the insertion of an electrode into the brain. Thus, it requires an invasive surgical procedure that necessitates making one or two holes in the skull. An electrode is placed in the desired region of the brain (in the case of PD usually the STN but also sometimes the globus pallidus); the electrode is connected to a wire that runs under the skin to a device called a pulse generator, which is usually implanted under the collar bone.

When the pulse generator is turned on, it emits electrical impulses that seem to disrupt neural functioning. This can be used to cause changes in brain activity that resemble what happens when a lesion has been created. Thus, implanting an electrode near the STN and turning on the pulse generator reduces excessive activity in the STN; the abatement of STN activity is associated with an improvement of symptoms.

Although the DBS procedure has seen some success in alleviating symptoms in patients with advanced PD, the mechanism by which it achieves those effects is still unclear. DBS in the STN does reduce STN activity in patients with PD, but it is uncertain why stimulation of a brain region would have effects similar to the ablation of that brain region. Several hypotheses have been put forth to explain the mechanism of DBS, ranging from the assertion that DBS causes changes in neurotransmitter and hormone levels to the proposition that DBS disrupts abnormal neural oscillations in the brains of PD patients. This latter hypothesis has perhaps received the most research attention as a mechanism of DBS, and is considered by some to be the most viable explanation.

Neural oscillations and phase-amplitude coupling

The term neural oscillations describes rhythmic changes in the electrical activity of neurons and can involve fluctuations in the membrane potential of an individual neuron (i.e. action potential) or a small population of neurons (i.e. local field potential). These neural oscillations in certain areas of the brain tend to exhibit patterns of synchronization, which means that the activity of different neural populations becomes regulated on a similar timescale. In other words, synchronized neural populations may (on average) fire action potentials at the same time, then be at rest at the same time. It is thought that these synchronized patterns of neural activity are used to facilitate communication and integrate activity among groups of neurons from different parts of the brain, and thus normal oscillatory behavior may be essential for diverse functions ranging from sensory perception to motor movements

There are several different rhythms of oscillatory activity that can be detected throughout the brain; they range from low frequency delta oscillations (1-4 Hz) to high frequency gamma oscillations (>30 Hz). What makes understanding the effects of neural oscillations even more complicated is that these different frequencies of oscillations can be linked, or coupled, together in such a way that different areas of the brain with different patterns of oscillatory activity seem to work in concert with one another by coordinating their disparate oscillatory behavior. For example, a peak in the activity in one region might coincide with a valley in the activity of another. This mechanism, known as phase-amplitude coupling (PAC) may allow for the syncing of activity across a variety brain regions in a dynamic manner, and is becoming recognized as a key feature of healthy cognition.

Deep brain stimulation as a correction to abnormal oscillatory activity

Patients with PD display abnormally increased oscillatory activity in the STN in the beta frequency (13-30 Hz), which has been hypothesized to disrupt the normal functioning of the basal ganglia in such a way as to impair movement. And, some studies have found that the reduction of this oscillatory activity may be one mechanism by which DBS alleviates the symptoms of PD. However, the signal for voluntary movement originates in the motor areas of the cerebral cortex, and it remains unclear how abnormal beta oscillations in the basal ganglia might influence the motor cortex in such a way as to produce the movement-related symptoms of PD. Thus, it is also unknown how the stimulation provided by DBS might affect the motor cortex to alleviate those symptoms.

In a recent study published in Nature Neuroscience, de Hemptinne et al. (2015) explored the hypothesis that DBS helps to improve the symptoms of PD by reducing excessive coupling of neural oscillations in the motor cortex. In non-PD patients, PAC between high- and low-frequency oscillations in motor areas of the brain occurs when at rest and is reduced when movements are made. It has been suggested that this coupling may inhibit neural activity until movement is initiated; at that point the coupling is diminished so movement can occur. de Hemptinne et al. hypothesized that in PD patients, the PAC is exaggerated and continues to inhibit movement even when a movement is desired. DBS, however, may act to reduce PAC and increase the possibility of movement execution. To test this hypothesis, they used a procedure called electrocorticography in PD patients before, during, and after DBS stimulation of the STN.

Electrocorticography (ECoG), also sometimes called intracranial electroencephalogram (iEEG), involves the placement of electrodes directly on the surface of the brain to record the electrical activity of neurons. Although this is an invasive surgical procedure, the patients in the study by de Hemptinne et al. were already undergoing surgery for the placement of the DBS electrode and thus an additional surgical procedure wasn't required. In this study, the electrodes for ECoG were placed directly on the sensorimotor cortex.

As the authors hypothesized, the ECoG recording before the DBS device was turned on showed excessive beta frequency activity in the STN as well as exaggerated coupling of beta activity with gamma frequency oscillations in the motor cortex. Patients at this point displayed characteristic PD symptoms like rigidity, tremor, and bradykinesia. When the DBS device was turned on, however, the abnormal PAC in the motor cortex was reduced and symptoms were alleviated. Additionally, the degree to which PAC was reduced was associated with the degree to which the patients' symptom severity was mitigated. Thus, it appears plausible that DBS reduces PD symptoms in part by reducing PAC in the motor cortex.

DBS is still considered a last-resort option for most PD patients, as it does involve invasive surgery and all the associated risks, and it is not successful for everyone. However, if we can come to fully understand the mechanism by which it works, we may be able to refine the method and improve its success rate. For example, if PAC in the motor cortex is to blame for the severity of some of the symptoms of PD, future DBS devices could incorporate real-time monitoring of PAC and the automatic adjustment of stimulation to most effectively reduce it.

As we uncover more information about the mechanism of DBS, it may become a treatment for PD that can eventually replace L-DOPA which, despite its therapeutic value, remains a temporary solution to the problem. Regardless of the improvements we make to DBS, however, it still does not seem it will be capable of permanently arresting the neurodegeneration that occurs in PD. Thus, the search will continue for a therapeutic approach to treating the symptoms of PD that can at the same time either slow or stop the relentless loss of basal ganglia neurons that defines the disease.

de Hemptinne, C., Swann, N., Ostrem, J., Ryapolova-Webb, E., San Luciano, M., Galifianakis, N., & Starr, P. (2015). Therapeutic deep brain stimulation reduces cortical phase-amplitude coupling in Parkinson's disease Nature Neuroscience, 18 (5), 779-786 DOI: 10.1038/nn.3997

2-Minute Neuroscience: The Hippocampus

In this video, I cover the hippocampus. I discuss its location in the temporal lobe as well as the other structures that surround it and make up the hippocampal formation, such as the dentate gyrus and hippocampal gyrus. I also describe the flow of information through the hippocampus, starting at the entorhinal cortex and traveling through the dentate gyrus, hippocampus, subiculum, and then to several different pathways and areas.

2-Minute Neuroscience: Thalamus

In this video, I cover the thalamus. I discuss the function of the thalamus as a relay station for information that is traveling to the cerebral cortex. I also cover some of the major nuclei of the thalamus, including the ventral posterolateral nucleus (VPL), ventral posteromedial nucleus (VPM), pulvinar nucleus, medial geniculate nucleus, lateral geniculate nucleus, and reticular nucleus.

Know your brain: Orbitofrontal cortex

Orbitofrontal cortex (in green)

Orbitofrontal cortex (in green)

Where is the orbitofrontal cortex?

The orbitofrontal cortex is the area of the prefrontal cortex that sits just above the orbits (also known as the eye sockets). It is thus found at the very front of the brain, and has extensive connections with sensory areas as well as limbic system structures involved in emotion and memory.

What is the orbitofrontal cortex and what does it do?

The orbitofrontal cortex (OFC) is a poorly understood area of the brain, but also one that inspires a great deal of interest for some of the roles it is hypothesized to play in higher-order cognition like decision-making. Indeed, the prefrontal cortex and frontal lobes in general are considered essential for rational thought, reasoning, and even the full expression of personality. Thus, much of the research into the OFC has focused on functions that seem especially important to the thought processes that separate humans from other species with "lesser" cognitive abilities. We know very little for sure about the OFC, however, and the degree to which the functions ascribed to it below are truly regulated by the OFC is still being debated.

Some of the functions commonly associated with the OFC--and indeed with prefrontal areas as a whole--involve impulse control and response inhibition. This hypothesized role for the frontal areas of the brain can be traced back to Phineas Gage, who allegedly experienced a drastic reduction in social inhibition after a railroad accident that caused extensive damage to his prefrontal and orbitofrontal cortices. Deficits in response inhibition have also been seen in human patients and non-human primates that have damage to the OFC. For example, in one experiment patients with OFC damage were rewarded by touching a particular image when it appeared on the screen of a video monitor, but taught to avoid touching a different image. Although they were able to learn to avoid one image initially, when the researchers reversed the value of the images (such that the once-rewarding image was now the one to avoid), participants with OFC damage had difficulty inhibiting their impulse to touch the previously-rewarding image. This may suggest that the OFC is concerned with a type of impulse control; however, others have argued that the OFC might only be involved in inhibiting impulses after this specific type of reversal procedure, as studies that have attempted to show a general deficit in response inhibition after OFC damage have not been consistent.

The OFC is also frequently associated with certain types of decision-making. For example, it has been hypothesized that the OFC is important in decisions that must be made by comparing the relative value among several options to decide which is preferable. Patients with damage to the OFC have been found to display deficits in gambling tasks that require them to consider the usefulness of different gambling strategies to maximize the potential of earning fake money. A study in monkeys also found that neuronal firing patterns in the OFC changed depending on the value of a juice reward the monkeys were offered (e.g. some neurons were activated more in response to being offered a rewarding Kool-Aid drink than in response to water). Later research has suggested the OFC may have a more specific role than just value-based decision-making; it has been hypothesized the OFC may be necessary for making predictions about decisions based on newly-learned information. In other words, the OFC might not be needed to form a simple association between a stimulus and a reward, but may be necessary if something changes about the stimulus and an estimate must be made about its potential to still provide a reward.

The OFC has also been implicated in playing a significant role in emotion. As mentioned above, the OFC is interconnected with limbic system structures like the amygdala, which are considered to be important to the experience of emotion. It has been hypothesized that the OFC is involved specifically in modulating bodily changes that are associated with emotion (e.g. a nervous feeling in the stomach and increased perspiration linked to anxiety). This hypothesis has been supported by experiments with patients who have OFC damage; in gambling tasks they tend to make risky choices and yet display no signs of anxiety as measured, for example, by skin conductance (which gauges perspiration). Healthy controls make fewer risky choices and when faced with the option of making a risky choice they display increased skin conductance, which suggests they are perspiring slightly. The patients with OFC damage can identify which choices are the most risky, yet they continue to make them. Researchers have suggested this is because the OFC is involved in providing an important bodily signal that helps individuals identify a poor choice by initiating an emotional response to it. Others have argued, however, that the deficits observed in gambling tasks with OFC-damaged patients represent a deficit that may not necessarily be emotionally-based or involve only emotionally-guided decisions. Indeed, patients with OFC damage don't seem to display a global emotional deficit, which might be expected if the OFC played a crucial role in regulating emotions.

Thus, although the functions discussed above have all been associated with the OFC, there is still a great deal of uncertainty as to the extent they are controlled by the OFC; at this point there is no consensus on what the OFC does and does not do. It seems safe to say that the OFC plays an important role in cognition, but it will take further research to determine what exactly that role is.

Stalnaker, T., Cooch, N., & Schoenbaum, G. (2015). What the orbitofrontal cortex does not do Nature Neuroscience, 18 (5), 620-627 DOI: 10.1038/nn.3982

Limitations of the consensus: How widely-accepted hypotheses can sometimes hinder understanding

To those of us who believe strongly in the scientific method, it really is the only approach to understanding the relationship between two events or variables that allows us to make assertions about such relationships with any confidence. Due to the inherent flaws in human reasoning, our non-scientific conclusions are frequently riddled with bias, misunderstanding, and misattribution. Thus, it seems there is little that can be trusted if it hasn't been scientifically verified.

The scientific method, however, is a human creation as well, and therefore it is less than perfect; at the very least our use of it is flawed due to the fact that human foibles inevitably creep into the process of innovation. One example of this can be seen when we mix our enticement to make scientific discoveries with financial incentives. When this occurs it makes the likelihood of malfeasance much higher, and causes tainted results to be a more distinct possibility. But there are many other examples of flaws in the scientific process that are a bit more subtle--and certainly less heinous--than fiscally-influenced dishonesty. Another pitfall, for instance, stems from the natural human bias toward favoring the familiar, understandable, and available ways of explaining a phenomenon over those that are less so.

This cognitive bias is generally most detrimental to the understanding of phenomena that are, as of yet, not well understood. For, when we gain some insight that we believe helps us to illuminate the mechanism underlying a poorly-understood phenomenon, we tend to build off of that insight. It serves as the foundation for many closely-related hypotheses and experiments to test those hypotheses. If these experiments are generally supportive of the new perspective, then our understanding of the phenomenon begins to form around that viewpoint. The new perspective then becomes the widely-accepted way of thinking about the phenomenon.

This may be fine if the newly-devised hypothesis ends up being indisputably accurate, as there is nothing wrong with building off of previous ideas to further overall understanding--indeed, this is the way the growth of human knowledge generally works. The problem occurs, however, when a sense of unanimity develops around the new hypothesis. This widespread agreement then can tend to limit the creative exploration of other mechanisms: it may make us quicker to disregard a competing hypothesis, less capable of obtaining grant funding to explore one, and sometimes less likely to pay attention to shortcomings in the consensus hypothesis itself. Thus, if a consensus hypothesis does not tell the full story (which often they do not), its acceptance may actually hinder scientific progress.

The dopamine hypothesis of schizophrenia

The dopamine hypothesis of schizophrenia is arguably a good example of this conundrum. Schizophrenia is a complex disorder that affects over 21 million people worldwide, but it can manifest in a drastically different way from patient to patient. It is characterized by a diverse group of symptoms that generally involve some detachment from reality, disordered thought processes, and/or impaired social interaction or withdrawal. The symptoms are commonly grouped as negative symptoms, which involve the absence of typical behaviors (e.g. limited speech, lack of affect), and positive symptoms, which involve the presence of unusual behaviors (e.g. hallucinations, delusions). Adding to the byzantine nature of the disorder, there are at least five subtypes of schizophrenia that distinguish schizophrenics by general trends in symptomatology. For example, paranoid schizophrenics often experience delusions of persecution along with hallucinations, while catatonic schizophrenics display a predominance of negative symptoms that include lack of movement, motivation, and emotion. Generally, the first clear symptoms of schizophrenia emerge in adolescence or adulthood in the form of an initial break with reality called a psychotic episode. The course of the disorder, however, is variable; some patients experience recurring psychotic episodes followed by remission of symptoms, while others suffer from constant symptoms that severely impact cognition and functioning on a daily basis.

The dopamine hypothesis of schizophrenia was formulated in the 1960s when it was discovered that drugs that can be used to treat schizophrenia also act as dopamine receptor antagonists. Because these drugs--which as a class are referred to as antipsychotics or neuroleptics--help to alleviate the positive symptoms of schizophrenia, it was assumed that the mechanism underlying schizophrenia must involve an increased level of dopamine neurotransmission. In other words, if antipsychotic drugs block dopamine activity and improve schizophrenic symptoms, then those symptoms must be caused by too much dopamine activity. Dozens of dopamine antagonist antipsychotic drugs have been developed since the 1960s with this reasoning in mind.

Further support for the dopamine hypothesis of schizophrenia was inferred from a phenomenon known as stimulant-induced psychosis. In some individuals who don’t have a history of psychosis, when high doses of stimulant drugs like amphetamine are taken (or even when normal doses are administered over long periods of time), the effects of the drugs appear similar in some ways to a psychotic episode. Because the drugs that can have this effect include as one of their primary mechanisms of action the increasing of dopamine levels, researchers suggested this strengthened the hypothesis that high dopamine levels are associated with schizophrenia. That is, if increasing dopamine levels through drug use can cause something that resembles a psychotic episode then it is likely psychotic episodes that occur naturally are also due to high dopamine levels.

Bolstered by these pieces of evidence, the dopamine hypothesis has guided schizophrenia research and drug development until the present day--and continues to do so. Over that time, additional research that supports the hypothesis has accumulated. For example, when amphetamine is administered to schizophrenic patients, the patients display greater increases in dopamine levels in response to the drug than healthy controls do. This supports the hypothesis that dopamine neurotransmission is dysregulated in schizophrenic patients, and suggests it may be elevated at baseline. Schizophrenic patients have also been found to have altered presynaptic dopamine function, including an increased capacity for dopamine synthesis and increased dopamine release from presynaptic neurons. The number of studies that have supported the hypothesis that dopamine signaling in schizophrenic patients is abnormal is actually quite extensive.

Regardless, serious questions about the role of dopamine in schizophrenia remain. Some still argue it isn't clear that there are dopaminergic abnormalities in the brains of schizophrenic patients, but even if we accept the premise that there are it remains undetermined if these differences in dopamine activity are the primary cause of the symptoms of schizophrenia. Despite the fact that antipsychotic drugs reduce activity at dopamine receptors, approximately 1/3 of schizophrenic patients don't respond to most antipsychotics. This suggests that some other mechanism must be at play in at least a significant minority of patients. Also, dopaminergic abnormalities alone don't seem to explain the negative symptoms of schizophrenia, as these are more resistant to the therapeutic effects of antipsychotic drugs than positive symptoms are. Indeed, some evidence even suggests negative symptoms may be improved by increasing dopamine levels. Furthermore, antipsychotics vary significantly in their affinity for the dopamine receptor, and that affinity doesn't always predict the clinical effectiveness of the drugs. Some antipsychotics have an affinity for serotonin receptors as well, and in some cases serotonin receptor affinity can predict clinical effectiveness, which suggests a role for the serotonin system in the mechanism underlying schizophrenia. And direct evidence for the hypothesis is lacking; when brains have been studied post-mortem or cerebrospinal fluid has been sampled to test for excessive dopamine activity, the results have been inconsistent.

These shortcomings have prompted a number of revisions of the dopamine hypothesis. For example, it has now been suggested that schizophrenia is characterized by both excessive dopamine transmission and low dopamine activity in different areas of the brain. According to this perspective, dopamine underactivity is associated with negative symptoms and overactivity with positive symptoms. Some researchers, however, have begun to consider other neurotransmitter systems as playing a central role in schizophrenia. One hypothesis that is gaining considerable support suggests that there is reduced glutamate activity in the brains of schizophrenics. This glutamate hypothesis doesn't argue that dopamine activity is normal in schizophrenia, but rather that glutamate dysfunction may play an equally important role.

Thus, after 40 years or so of the dopamine hypothesis guiding schizophrenia research, more and more investigators are now considering it to be unlikely dopamine dysfunction fully explains schizophrenia. Of course, it would make sense that such a complex disorder cannot be explained by fluctuations in the levels of just one neurotransmitter. In fact, if the dopamine hypothesis had been devised today, it may have had a more difficult time gaining such widespread support, as the field of neuroscience is now much more wary than it was a few decades ago of explanations for complex disorders that focus primarily on one neurotransmitter (or one gene, brain region, etc.); we have learned from experience that these explanations often end up being gross oversimplifications.

But has the dopamine hypothesis hindered our understanding of schizophrenia? It's really impossible to know for sure. When one hypothesis dominates an area of research for a prolonged period of time, however, it usually does have a significant influence on that research. Widespread acceptance of the hypothesis can create a situation where challenges to it become less frequent, and competing hypotheses are often not given as much attention. Researchers may even find it easier to get grants funded when those grants involve an investigation of some aspect of the well-known hypothesis than when they involve venturing out into less familiar territory. This can have a restrictive effect on research, causing it to be more difficult to explore alternative hypotheses and thus actually making the consensus hypothesis more popular by default (because there are no viable alternatives). Thus, perhaps if the dopamine hypothesis hadn't had such extensive support, we would have seen competing perspectives like the glutamate hypothesis garner attention earlier on.

Additionally, when there is a consensus hypothesis, investigators may be more likely to disregard research results that disagree with it. After all, if everyone knows high dopamine levels cause schizophrenia, then there must be something wrong with the methods of an experiment that indicates otherwise. This type of thinking can contribute to publication bias, a tendency to only publish favorable results and discard findings that don’t support one’s hypothesis. This type of bias can serve to further propagate a consensus hypothesis as potentially contradictory research results are considered quirky aberrations instead of leads worth following. Schizophrenia research doesn't display clear evidence of a large influence of publication bias, but it doesn't seem to be completely clear of its influence, either.

Regardless, one could argue that a concentrated focus on one hypothesis is an important part of scientific investigation. It allows for the organization of our thoughts, and through the reduction of a complicated process into its component parts, helps us to make sense of at least a portion of what is going on. Successful experiments supporting a consensus hypothesis may also inspire increased experimentation in and attention to an area of research, which in and of itself may speed up the process of coming to understand a phenomenon more fully.

However, even if there are benefits to this increased focus, it may be best to still maintain that focus with the caveat in mind that just because a hypothesis is widely accepted does not mean it is correct. It may be useful to constantly remind ourselves that we still know very little about neuroscience, and that in most cases the simpler the hypothesis seems to be, the more likely it is to be lacking. Continuing to seek out greater complexity instead of focusing all our efforts on finding support for an easy-to-explain mechanism may allow us to avoid falling into the trap of the consensus hypothesis, which can in some ways limit the ability of our understanding to grow.

Moncrieff, J. (2009). A Critique of the Dopamine Hypothesis of Schizophrenia and Psychosis Harvard Review of Psychiatry, 17 (3), 214-225 DOI: 10.1080/10673220902979896

Know your brain: Cochlea

Where is the cochlea?

cochlea and cochlea in cross-section. image courtesy of openstax college.

cochlea and cochlea in cross-section. image courtesy of openstax college.

The cochlea is a coiled structure that resembles a snail shell (cochlea comes from the Greek kochlos, which means "snail"); it is found within the inner ear. It is a small--yet complex--structure (about the size of a pea) that consists of three canals that run parallel to one another: the scala vestibuli, scala media, and scala tympani.

What is the cochlea and what does it do?

When sound waves travel through the canal of our outer ear, they hit the tympanic membrane (aka eardrum) and cause it to vibrate. This vibration prompts movement in the ossicles, a trio of tiny bones that transmit the vibration to a structure called the oval window, which sits in the wall of the cochlea. The ossicle bone known as the stapes taps on the oval window to pass the vibration on to the cochlea, all the while using a fine-tuned movement that preserves the frequency of the original sound wave that hit the eardrum.

The cochlea is filled with fluid. Specifically, the scala vestibuli and scala tympani contain a fluid called perilymph, which is similar in composition to cerebrospinal fluid, and the scala media contains endolymph, which more resembles intracellular fluid in terms of its ionic concentrations. When the oval window is depressed by the stapes it creates waves that travel through the fluid of the cochlea, and these waves cause a structure called the basilar membrane to move as well.

The basilar membrane separates the scala tympani from the scala media. When waves flow through the fluid in the cochlea, they create small ripples that travel down the basilar membrane itself (to visualize these ripples imagine the basilar membrane as a rug someone is shaking out). The basilar membrane is structured such that different sections of the membrane respond preferentially to different frequencies of sound. As waves progress down the basilar membrane, they reach their peak and then rapidly diminish in amplitude at the part of the membrane that responds to the frequency of the sound wave created by the original stimulus. In this way, the basilar membrane accurately translates the frequency of sounds picked up by the ear into representative neural activity that can be sent to the brain.

hair cells (on right). image courtesy of openstax college.

hair cells (on right). image courtesy of openstax college.

The translation of the movement of the basilar membrane into electrical impulses occurs in the organ of Corti, which is the receptor organ of the ear. It sits atop the basilar membrane and contains around 16,000 receptor cells known as hair cells. Hair cells are so named because protruding from the top of each cell is a collection of somewhere between 50 and 200 small "hairs" called stereocilia. Hair cell stereocilia have fine fibers, known as tip links, that run between their tips; tip links are also attached to ion channels. When the basilar membrane vibrates, this induces movement of the hair cells, which causes the tip links to pull open the associated ion channels for a fraction of a millisecond. This is long enough to allow ions to rush through the ion channels to cause depolarization of the hair cell. Depolarization of hair cells leads to a release of neurotransmitters and the propagation of the auditory signal. The vestibulocochlear nerve will carry the information regarding the auditory stimulus to the brain, where it will be analyzed and consciously perceived.

Møller, A. (1994). Auditory Neurophysiology Journal of Clinical Neurophysiology, 11 (3), 284-308 DOI: 10.1097/00004691-199405000-00002