In the open field paradigm, an animal is placed in a large square box with walls. The animal (often a rodent, such as a rat or mouse) is free to move about the box for a set amount of time. The experimental design was developed by Calvin S. Hall.

The open field test is equipped with tools to track the position of the animal.. One method is to divide the area into a grid, with infrared beams projecting from one side to the other. If this beam is broken, then it indicates the animal had crossed from one square of the grid to the next.

A more sophisticated method to measure locomotion is to use a open field with an overhead camera. The camera is able to track more precisely the position of the animal, and can give a more accurate measure of distance traveled. Also, the overhead camera can quantify other behaviors such as rearing or defecation.

What does the open field test measure?

The most robust measurement collected by the open field is locomotor activity. This is basically how much the animal moves around. Interpreting these data is straightforward, as higher locomotor activity counts means more movement.

In addition to measuring locomotion, an open field test is also used to evaluate anxiety in rats or mice. The idea is that rodents prefer to be surrounded rather than exposed out in the open. In other words, a rodent will naturally prefer to be close to the walls rather than being exposed in the center of the open field. Usually, behavioral researchers will define the middle third to be the center of the open field. It is an evolutionary maintained behavior to avoid predators which may be hunting in the open, so they tend to hug the walls which provide them a little bit of cover.

What variables affect open field performance?

Mice and rats are especially sensitive to new environments. The normal reaction many rodents exhibit when first put into a new place is exploration. They will spend a lot of time examining their environment when they are first placed into the open field apparatus. Therefore, the locomotor counts are usually higher at the beginning, then decrease as the animal feels more comfortable in their surroundings.

Animals that have received a psychostimulant (such as caffeine, cocaine, or amphetamine) prior to testing will show a greater number of beam breaks or locomotion, as they move around the box more than their saline treated counterparts.

If a rodent is given an anxiolytic drug (one that decreases anxiety; commonly drugs such as benzodiazepines like Xanax) then they will spend more time in the center of the open field as opposed to the sides (The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review). Antidepressants may also increase time spent in the center.

The open field test has been criticized because of it’s low ethological validity. Critics suggest that a flat terrain, four cornered environment does not resemble anything that a mouse or rat in the wild would experience.

How to interpret results from open field test

The most straightforward measures include the following variables:

1. Distance traveled. This is a measure of how far the animal had moved over the course of the testing protocol. Although rats and mice are small, they can travel somewhere around 20-30 meters in five minutes. When analyzing these data, you can expect these numbers to increase after psychostimulant exposure. On the other hand, these numbers decrease if the rat is given a sedative drug.

2. Time spent in center region as a fraction of total time spent. This is a measure for anxiety like behavior. These values are often expressed as a percentage; increases in the amount of time spent in the center suggest an anxiolytic effect. So, giving the mouse a drug such as a benzodiazepine may lead to decreased center time.

3. Number of entries into center region. This variable is also a measure of anxiety like behaviors. Once the region defined as the “center” has been defined, each entry into this center region counts as an event. More events observed indicate anxiolytic effect of the drug.

Drugs can be delivered into the body through several different routes of administration - oral, intravenous, and inhalation being the most common. Although the skin is very effective at keeping chemicals out, some chemicals are able to pass through the skin. Among those chemicals that do, the words “topical” and “transdermal” may be used. 

These two words are often mistakenly used for one another, but they have different meanings.

Differences between topical and transdermal

Topical medications are the kinds that we imagine have a local effect on the person. For example, these are often creams, lotions, or ointments. The most common topical medications are used to treat conditions like acne or eczema. A topical medication like Tiger-Balm or Icy-Hot acts at local circuits only, and they are useful for relieving pain or inflammation. In all these cases, the drug does not diffuse very far. It only moves around the tissue underneath where it is applied and has no effect on the central nervous system.

Transdermal medications, however, cross the skin and get absorbed into the bloodstream. Because these chemicals can enter the bloodstream, they can have an effect on several organs, including the brain. The common transdermal medications we may think of include a motion sickness patch, a nicotine patch for people who are trying to quit smoking, or a fentanyl patch for pain. Transdermal medications are more often used for chronic conditions.

Transdermal medications are so valuable because they provide a controlled release of the drug over time. Topical medications are usually used for short-term relief whenever symptoms are local. 

Compared with other routes of administration, dosing with transdermal medications is relatively simple since the application only needs to happen once. Some patch formulations are designed to last for several days. Topical drugs may need to be applied a few times a day.

In the nervous system, the color of the tissue gives information about the function of those areas of the brain. Gray matter contains mostly the cell bodies of neurons. On the other hand, white matter contains the axons of those neurons. White matter structures are mostly used for communicating information between major circuits of neurons.

Structure of the uncinate fasciculus

The uncinate fasciculus ia a long white matter tract. The fiber tract has one end in the pole of the temporal lobe, which is the part of the cortex behind the ears. Here, it is connected with many of the limbic structures, parts of the brain that are strongly involved with our processing of emotional states and memories. Some limbic structures connected with the uncinate fasciculus include the amygdala and parahippocampal gyrus. 

From there, the uncinate fasciculus curves upwards and anteriorly towards the frontal lobe. In the frontal lobe, the white matter fibers connect with other important structures like orbitofrontal cortex, one part of the prefrontal cortex. The orbitofrontal cortex is important when it comes to cognitive flexibility and learning appropriate responses.

The uncinate fasciculus is a bi-directional pathways, which means that axons are sent outwards from the temporal lobe and out of the frontal lobe.

The precise shape and angle of the uncinate fasciculus can be determined using an imaging method based on fMRI technology called diffusion tractography, or DTI. In DTI, the movement of water molecules are tracked, and this is used to differentiate white matter from gray matter.

Function of the uncinate fasciculus

The uncinate fasciculus is important for a wide range of congitive and emotional functions. Some functions include:

1.  Memory. The parahippocampal areas are important structures for the creation of memory related circuits, which are communicated towards the orbitofrontal cortex for more longer term storage. One specific type of memory attributed to uncinate fasciculus is reversal learning. In an example reversal learning experiment, a person may learn to push a button whenever they see a green stimulus to get a reward. After several successful trials, the person may need to NOT push the button when they see the green stimulus to get the reward. 

2. Emotional regulation. The circuits of the amygdala are important for the formation of emotionally related memories, such as creating associations between innocuous stimuli and pain. The related frontal lobe circuits are involved in impulse control and inhibition of behaviors. Being able to control an emotional outburst during distressing situations, for example, is a behavior that the uncinate fasciculus likely mediates.

3. Language. The inferior frontal gyrus (IFG) is a brain structure that has a strong role in the production of language. Within the IFG is an area called Broca’s area, which when damaged, produces a language disorder called expressive aphasia. Connections between the IFG and temporal lobe through the uncinate fasciculus is probably important for language related memories, such as when a person is learning new words.

Clinical implications of the uncinate fasciculus

1. Autism. Among verbal autistic people (diagnosis of autism spectrum disorder), there is a difference in uncinate fasciculus volume between the left and right hemispheres, while no hemispheric differences are found in either typically developing people or nonverbal autistic people. (Structural connectivity in ventral language pathways characterizes non-verbal autism)

2. Major depressive disorder. Brain imaging strategies have shown that decreased left uncinate fasciculus volume is correlated with major depressive disorder. (Reduced myelin density in unmedicated major depressive disorder: An inhomogeneous magnetization transfer MRI study)

3. Alzheimer’s disease. Using diffusion tensor imaging, it was discovered that the uncinate fasciculus had lower fractional anisotropy in patients with Alzheimer’s disease compared to age matched control participants. Fractional anisotropy is a measure of white matter degeneration. (Diffusion abnormalities of the uncinate fasciculus in Alzheimer’s disease: diffusion tensor tract-specific analysis using a new method to measure the core of the tract)

Morphology of cerebellar granule cells

The class of cells called “granule cells” are generally the smallest neurons in the brain. They often have diameters as small as 10 microns. Because of their small size, they can be densely packed close to one another.

Granule cells in the cerebellum only have a handful of dendrites where they receive synaptic input. They get excitatory inputs from the mossy fibers. They also get inhibitory inputs from Golgi cells. They send excitatory glutamatergic axonal projections up to the cerebellar cortex, where they split into two branches, forming the parallel fibers. These cells therefore have a distinctive T shape.

Functions of cerebellar granule cells

It has been difficult to determine their function during behavior. Because they are so densely packed, it becomes tricky to identify which cells are firing and which ones are not.

However, it is believed that these cerebellar granule cells are important for integrating incoming sensory information with outgoing motor information, implicating them in the context of implicit memory learning.

Also called von Frey filaments or von Frey hairs, von Frey fibers are a diagnostic tool designed for examining pain threshold at different parts of the skin. They were developed by Maximilian von Frey in 1896. The von Frey filament itself is a long, thin elastic nylon tube. It is pushed directly into the skin at a right angle. When a certain amount of pressure is applied, the von Frey fiber will buckle. Once the filament buckles, further application of pressure will not transmit any further force to the skin.

There are several von Frey fibers in each set. Each one is calibrated for a certain amount of force before it buckles. The force required before buckling is related to the diameter of the von Frey hair - the larger the diameter, the higher the force that must be applied before the filament buckles. Often times, that force ranges from .008 grams to 300 grams.

They are used as a diagnostic or assessment tool for examining pain threshold at the skin surface. A person with a high pain threshold will not respond to the low force fibers, as they do not perceive them as painful. However, someone with a low pain threshold may react to the low force fibers with a painful response such as withdrawal of the hand or by saying that the stimulus hurts. Because an experimenter is able to test a whole range of responses, the von Frey fibers are a useful diagnostic tool.

For example, people with allodynia, a condition that causes innocuous stimuli to be perceived as painful, have a very low pain threshold. They would withdraw their hand following the application of a low force von Frey filament. A related state is called hyperalgesia, when a person is more sensitive to painful stimuli, will result in withdrawal after application of a lower force fiber. On the other hand, a person with congenital insensitivity to pain would have a very high pain threshold, and would only respond to the high force von Frey filaments.

Recently, an electronic version of the von Frey hairs has been developed and tested in an animal model of chronic pain (Measuring Changes in Tactile Sensitivity in the Hind Paw of Mice Using an Electronic von Frey Apparatus). The electronic version provides a more objective and less disruptive method for analyzing pain threshold in animal models.

Several vendors make their own version of the von Frey pain threshold test, including Bioseb.

Animal tests using von Frey fibers

The von Frey test can also be performed on animals, such as rats and mice. In these experiments, a scientist would hold the paw of the rat or mouse, then press different stiffness von Frey fibers into the palm until the animal withdraws the paw. These animal studies are useful for answering several different types of questions, such as:

What are the cellular mechanisms behind congenital insensitivity to pain (CIP)? It has been demonstrated that a mutation that appears in CIP is related to the voltage-gated sodium channels. (Nav1.7 is required for normal C-low threshold mechanoreceptor function in humans and mice)

What novel drugs may be useful for helping people with chronic or neuropathic pain? New chemicals can be tested to see if they are useful in decreasing pain among animals with artificial pain conditions. As an example of how von Frey fibers can be used to answer this type of research question, see (Effect of Immature Rubus occidentalis on Postoperative Pain in a Rat Model)

Are different anesthesia protocols better? For example, the von Frey fibers can be used in veterinary medicine (Clinical and Antinociceptive Effects of Distal Inferior Alveolar Nerve Block in Ponies With Tramadol 5% or Lidocaine 2).

Recall that long term potentiation is the strengthening of synapses in response to repeated stimulation. LTP is an important process which models learning in the hippocampus. Alternatively, long term depression (LTD) is the weakening of synapses which accompanies little or no stimulation; LTD can be thought of as the inverse of LTP and plays an equally important role in establishing biological mechanisms for learning and memory. However, much less in known about the precise biological mechanisms of LTD.

Long term depression is not to be confused with major depressive disorder (MDD). LTD is a cellular mechanism which examines the nervous system at the level of synapses and cells. MDD is a clinical diagnosis that is made during a psychological assessment of a person using criteria set forth by the DSM-V and may be measured using one of several psychological tests, like the Beck depression index.

Though gaps in information do exist, there is a lot of information that has been discovered regarding LTD. LTD is generally discussed in two areas: the hippocampus and the cerebellum.

LTD in the cerebellum

LTD in the cerebellum is slightly more complex than its hippocampal counterpart. To understand the process entirely, we must first discuss the anatomy of the cerebellar cortex. The cerebellum receives input from the motor cortex and the spinal cord, and the cortex consists of three cellular layers: the granule layer, the Purkinje layer, and the molecular later. Granule cells lie in the granule layer, and their axons ascend into the molecular layer where they split and form parallel fibers. Purkinje cells reside in the middle layer, the Purkinje layer, and their dendrites form extremely complex structures seen in the molecular layer in image 1 above. The dendrites of the Purkinje cells line up with the parallel fibers and form synapses in the molecular layer.

There are two main forms of input to the cerebellum: climbing fibers and mossy fibers. Climbing fibers originate in the medulla, specifically, the inferior olive and travel to the Purkinje cell where the climbing fiber twists itself around the Purkinje cell dendrite and forms synapses. Action potentials from the climbing fibers generate EPSPs which activate the Purkinje cells.

The second input, mossy fibers, arise from the brain stem and synapse on granule cells. These granule cells, whose axons are parallel fibers ascending into the molecular layer where they encounter the Purkinje cell. Thus, there is a point where the parallel fibers and climbing fibers can simultaneously provide input to the Purkinje cells. This is the essential point for LTD.

Simultaneous activation of these pathways results in synaptic modifications of the Purkinje fiber. Climbing fiber activation depolarizes the Purkinje cell, and this activates calcium channels resulting in a calcium influx into the cell. On the other hand, parallel fiber activation has two outcomes. By releasing glutamate upon activation it can activate AMPA receptors on the Purkinje cells membrane, which results in a sodium influx into the Purkinje cell. The same glutamate release also stimulates metabotropic glutamate receptors, which activate phospholipase C. The activation of phospholipase C leads to the production of diacylglycerol which activates protein kinase C. Protein kinase C and calcium work together to decrease postsynaptic response of AMPA, which demonstrates the plasticity that is associated with LTD. This decrease in response results in the synaptic inefficiency that is characterized by LTD.

LTD in the hippocampus

As previously mentioned, long term depression is commonly discussed in two brain structures parts, the second being the hippocampus. The mechanisms of LTD here are less well understood and still under investigation. The lack of stimulation that occurs results in a weak depolarization of the postsynaptic neuron. In LTP, depolarization of the postsynaptic neuron results in a displacement of the magnesium block; however, in LTD, activation is not strong enough to displace the block and results in a small amount of calcium flowing into the cell. This calcium activates phosphatases which dephosphorylate proteins. LTD is associated with dephosphorylation and internalization of AMPA receptors, which leads to a decrease in synaptic efficiency similar to what is seen in the cerebellum.

The concept of LTD is extremely important, as it demonstrates a molecular model for synaptic plasticity - one of the most important capabilities of the brain. LTD is an essential concept for understanding the biological mechanisms of learning and memory. Though many of these mechanisms are still unclear and incomplete, ongoing research will likely provide more knowledge into specific aspects of this process.

Opioid painkillers, such as morphine, are commonly used in the clinic. These drugs work by blocking the sensation of pain through activating brain circuits that communicate with the spinal cord. When recovering from a major surgery, a patient might be given a morphine drip or a pill containing a slow release oxycodone. Both morphine and oxycodone are opiate drugs.

For many people, opioids are effective at blocking pain; they are the most effective analgesic drugs that are currently available. However, these drugs do not always work for everyone. Some people can take morphine and not experience a strong painkiller effect. For these people, a non opioid painkiller, such as ibuprofen or aspirin, may be more effective.

There are several possible reasons why this may happen.

Genetics of opioid processing enzymes

In a health care setting, it may be preferable to treat the patient with a less potent opioid medication, which may have lower addiction potential. Hydrocodone and tramadol fit this category, and are sometimes referred to as first-line opioids. 

After these drugs enter the bloodstream, they are processed by enzymes in the liver. One of the key enzymes used in opioid metabolism is a form of the cytochrome P450 called CYP2D6. When this enzyme interacts with hydrocodone or tramadol, it creates a byproduct with significant opioid activity. These byproducts actually have a stronger ability to bind to and interact with the opioid receptors than the original compound. Due to random variations in genetic sequences, some people have a version of the CYP2D6 enzyme that is less effective. For these people, a higher dose of the opioid is needed before they experience the same degree of analgesia (Impact of CYP2D6 Pharmacogenomic Status on Pain Control Among Opioid‐Treated Oncology Patients). 

Closely related is another liver enzyme called UGT2B7. Morphine is processed by the UGT2B7 enzyme into two different compounds. One of them, called M3G, has no activity at the opioid receptors. If a person has a genetic mutation in the UGT2B7 gene, they may process morphine into M3G quicker, meaning that morphine exists for less time in the blood. Another result of the morphine metabolism is a different chemical called M6G, which is actually a better analgesic than morphine. Mutations of the enzyme may again influence a person’s response to opioids.

These genetic components are entirely out of a person’s control. 

Previous exposure to opioids leading to tolerance

When a person is exposed to a drug repeatedly, they may develop a tolerance. Tolerance is a change of the body where a person needs to take more drug to experience the same effect. People can develop tolerance if they use opioid drugs recreationally, whether it is heroin or a prescription. 

Tolerance happens at the level of receptors. Opioid painkillers bind to receptors throughout the nervous system. When a person regularly takes opioid drugs, the cells expressing the receptors may downregulate the receptors, making them less sensitive to other opioids. So, when a person is given more opioid painkiller, the downregulated receptors makes it so the person needs a higher dose to experience the same degree of analgesia.

In the central nervous system, the main excitatory neurotransmitter is glutamate. Glutamate signals to the postsynaptic cell by activating different types of receptors. Although there are several glutamate receptors, two important types are called the AMPA receptors and NMDA receptors. These have been named because they can be selectively activated by the chemicals α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA), respectively.

Both of these receptors are critically important for healthy nervous system function, and dysregulation of these receptors is known to lead to a variety of psychiatric conditions, ranging from schizophrenia (Ketamine as a pharmacological tool for the preclinical study of memory deficit in schizophrenia) to epilepsy (GRIN2A-related epilepsy and speech disorders: A comprehensive overview with a focus on the role of precision therapeutics).

Similarities between AMPA and NMDA receptors

AMPA and NMDA receptors bind to and are activated by the neurotransmitter glutamate

Glutamate is the most common neurotransmitter in the entire human brain. Glutamate is an amino acid that the body is not able to produce on its own. Much of the glutamate our body uses comes from dietary sources like glutamine. Glutamine is taken into presynaptic cells, where an enzyme called glutaminase converts it into glutamate, which is then packaged into vesicles for release. Glutamate is also converted by enzymes in glia.

During an action potential, glutamate is released into the synapse. These molecules then diffuse across the synapse, where they can bind to a specific location on the AMPA or NMDA receptors.

AMPA and NMDA receptors are non-selective cation channels

Both AMPA and NMDA glutamate receptors are transmembrane ion channels. This means that their protein structure is embedded within the cell membrane and has a special pore that allows ions to pass across into or out of the cell. Once a molecule of glutamate binds to and activates their AMPA or NMDA receptors under certain conditions, the receptors physically change shape. This causes the pore to open up. Now, cations can move across the cell membrane. 

AMPA and NMDA receptors are non-selective cation channels, which mean that they let sodium (Na+) and potassium (K+), and in some cases, calcium (Ca2+) cross the cell membrane.

AMPA and NMDA receptors are both excitatory

When a molecule of glutamate activates the AMPA or NMDA receptors, the result of ion channel opening is flow of positively charged ions. Generally, the ion that moves across the cell membrane the most is sodium. Specifically, sodium wants to enter into the cell. 

There are two reasons sodium wants to move into the cell. One is that it wants to move down its chemical gradient. There is a much higher concentration of sodium outside the cell compared to inside, roughly ten times more. Ions want to be an area of low concentration, if possible.

The second reason is that the inside of the cell is usually negatively charged. Sodium carries a positive charge, so it is attracted to the negative charges inside the cell.

When sodium enters into the cell, it carries a positive charge. This charge makes the cell membrane become more positive, thereby depolarizing it and bringing the cell closer to the action potential threshold. Therefore, activation of these receptors make the cell more likely to fire an action potential.

Differences between AMPA and NMDA receptors

AMPA receptors may or may not be calcium permeable. NMDA receptors are calcium permeable.

Although both glutamate receptors are cation permeable and therefore excitatory, calcium may or may not be the charge carrying cation that enters the cell through these receptors. For AMPA receptors, their ability to pass calcium depends on the subunits that make up the receptor. AMPA receptors are made up of four subunits per channel. If an AMPA receptor contains the subunit GluR2, the properties of the pore change so that the receptor is calcium permeable. Many AMPA receptors do not contain a GluR2 subunit, and these AMPA receptors are calcium impermeable.

But, NMDA receptors are intrinsically permeable to both sodium and calcium, regardless of the subunits that make up the receptor.

NMDA receptors, but not AMPA receptors, can be blocked by magnesium ion

The concentration of magnesium in the extracellular space of a mammalian cell is relatively low, roughly 1 millimolar. However, the magnesium ion (Mg2+) is a large and bulky ion that can interfere with passage of other ions through the NMDA receptor. The AMPA receptor does not have space for Mg2+ to block the pore.

NMDA receptors are more involved with synaptic plasticity 

Synaptic plasticity is believed to be the underlying cellular mechanism that explains complex behavioral phenomena such as learning or memory. At the level of neurons, examples of synaptic plasticity include long-term potentiation, the persistent strengthening of a synapse, and long-term depression, a weakening of a synapse.

These cellular observations are likely a consequence of NMDA receptor activation. Through a series of signaling molecules, activation of NMDA receptors under depolarizing conditions cause an influx of calcium ions, which trigger activation of enzymes such as CaMKII. This molecule can then signal through a variety of mechanisms to enhance synaptic strength.

These findings were demonstrated in a Nature publication from 1995 (Distinct components of spatial learning revealed by prior training and NMDA receptor blockade), where the researchers discovered that performance on the Morris water maze worsened became worse after treatment with an NMDA receptor antagonist.

The pork tapeworm Taenia solium is a parasite that can live in the human body. When the infection spreads to the central nervous system, it is called neurocysticercosis. The infection begins when a person ingests the tapeworm eggs, which are often found in contaminated food and water. Once inside the body, the tapeworm undergoes their life cycle. The eggs hatch into larvae which can migrate into the brain. The larvae form cysts, which leads to many different symptoms.

Symptoms of neurocysticercosis

The most common immediate symptom are headaches. These may be accompanied by nausea and vomiting. All of these likely occur because of the widespread inflammation of the nervous system, particularly to the meninges, which are the layers of membrane that surround the brain and spinal cord. Inflammation leads to compression of the brain tissue.

New onset of adult seizures without a diagnosis of epilepsy is another symptom. These seizures can be minor, such as an absence seizure, which appears as if a person is suddenly staring and unresponsive. However, in severe cases, neurocysticercosis can cause grand mal seizures, which cause muscle convulsions and loss of balance. Many different types of seizures can happen in neurocysticercosis.

Cognitive impairment may also result from infection. This may include a difficulty with memory and attention. These symptoms make it difficult for the patient to perform their daily activities.

Other symptoms include difficulty with coordination, balance, and vision. 

Symptoms can range in severity. If gone untreated, they may last for months and years. The most severe cases of neurocysticercosis result in permanent brain damage or death.

Diagnosing and treating neurocysticercosis

Diagnosing neurocysticercosis can be difficult, since the reported symptoms are often common across many other more common conditions, such as meningitis. Some people also have no symptoms.

Neurocysticercosis may be detected with structural imaging of the brain, such as a CT scan or MRI scan. Both of these are capable of detecting the cysts in the brain tissue.

A serological test can also be done by taking a sample of blood. A person with a tapeworm infection will start producing antibodies against the parasite, and the presence of these antibodies in the blood suggest an underlying infection.

The treatment for the infection is to remove the parasite from the body. A class of drugs called “antihelminthics” are often used for this purpose. Albendazole is one example of an antihelminthic that may be diagnosed for treatment of the tapeworm larvae. 

These are often prescribed alongside corticosteroids to help reduce the inflammation.

Epidemiology and causes of neurocysticercosis

Neurocysticercosis is rare in the United States, but it is a public health problem in many developing countries around Latin America, Africa, and Asia.

Prevention measures against neurocysticercosis are aimed at decreasing exposure to the tapeworm and minimizing transmission in the first place. Generally, this includes fully cooking pork products, thoroughly washing vegetables, and good hygiene practices such as handwashing.

Antiepileptic drugs (AEDs) are widely prescribed to help treat patients with epilepsy or other difficult to diagnose seizure disorders. They are sometimes called anticonvulsants. Since epilepsy leads to uncontrolled activity of the brain’s neurons, decreasing the activity of these neurons can help patients keep their symptoms under control, allowing them to live a normal life. Many antiepileptic drugs therefore act to decrease cellular excitation. 

Antiepileptic drugs can be taken in several forms, including pills and tablets. These types of medications are most effective when taken regularly. It may be difficult to predict which dosage is most effective, so the doses may be adjusted on a trial-and-error basis. Some drugs can also be injected, but these are not very common and reserved for use in a hospital. 

There are several different mechanisms that these drugs may use to treat patients. 

Antiepileptic GABA drugs

One neurotransmitter system that is targeted by anticonvulsants is GABA. GABA is widely used across many synapses in the brain. This neurotransmitter is responsible for inhibiting neuronal activity, and the activity of many neurons is regulated by release of GABA. When a molecule of GABA binds to its receptors, called GABAA and GABAB, it decreases the likelihood that the neuron will fire an action potential. By increasing the activity of GABA, antiepileptic drugs decrease overall action potential activity of the brain, which can decrease the severity and the likelihood of seizures. 

One of these drugs is valproate (also called valproic acid), although its effect on GABA signaling is just one of many mechanisms that result in dampened brain activity. Topiramate, a different antiepileptic drug, targets the GABAA receptors as a way to decrease seizures.

Some benzodiazepine drugs help decrease seizure frequency through modifying GABA pathways. These influence neurons by acting as positive allosteric modulators, which increase the intensity of the GABA signal whenever GABA is bound to the receptors. Midazolam and lorazepam are two example benzodiazepine drugs that are prescribed as anticonvulsants.

Antiepileptic voltage-gated sodium channel blockers

It is believed that excess firing of action potentials across neurons leads to seizure activity. For an action potential to take place, neurons need to receive strong excitatory input. When that excitation reaches a threshold, a population of receptors in the cell membrane, called voltage-gated sodium channels, open. These channels cause the cell to depolarize, causing the release of neurotransmitters. 

Therefore, some classes of antiepileptic drugs can target these voltage-gated sodium channels, changing their properties so that fewer action potentials are fired. Some examples of these drugs include carbamazepine and lamotrigine.

Antiepileptic glutamate antagonists

Glutamate is the main excitatory neurotransmitter, meaning that it increases the activity of nerve cells in the brain. By blocking glutamate signaling, antagonist drugs reduce the likelihood of seizures. The most common molecular targets for glutamate antagonists are the AMPA and NMDA types of receptors.

An example of a glutamate antagonist drug used for treating epilepsy is perampanel. 

Side effects of antiepileptic drugs

Since AEDs decrease overall brain activity as a means to control seizure activity, many AEDs have side effects. Common side effects include drowsiness, dizziness, and nausea. Some of them may impair memory, since strong neuronal activity can promote the strengthening of synapses (long-term potentiation), which is the cellular foundation of learning. More serious side effects may include allergic reaction, liver damage, or psychiatric changes. Before being put on AEDs, it is a good idea to ask your healthcare provider about the side effects of the drugs. In all cases, patients should be carefully monitored once starting treatment with AEDs.

What if the antiepileptic drugs don't work for me?

AEDs may not work for everyone. It is estimated that antiepileptic medications are effective for around 70% of patients. But for the remaining 30% of patients, the medications, even when properly dosed and titrated, do not treat the symptoms.

In severe cases of epilepsy that is not responsive to medications, more radical approaches like surgery may be suggested. The purpose of these surgeries is to remove the neurons that are responsible for starting the unusual electrical activity. Alternatively, surgery may be done to destroy the tissue that allows for a “feedback echo” of electrical firing. Usually, this is done by cutting the corpus callosum, the large white matter tract that connects the left and right hemispheres.

One component of psychology is to try to measure a variety of traits of people, and simplify them into an easily understood spectrum. Jeff McCrae and Paul Costa developed the Five Factor Model (FFM) of personality to try to evaluate personality.

Big Five Aspect Scales (BFAS) is one way to determine where someone falls on the Big Five personality measures. It is a 100-question self-report test that is open source, and can easily be accessed online. Many versions of the test are graded on a Likert scale, so for each statement, the respondent will choose how much they disagree or agree on a scale from 1 to 5.

For each of the five measures, a person may either score high, low, or somewhere in between. The interpretation of each score is not always well defined.

The “Big Five” measures consist of the following (In some surveys, these scales may be ordered to form the acronym OCEAN):

Neuroticism

People who score low on the neuroticism scales can be described as being relaxed, easy-going, unemotional, resilient, or confident. On the other hand, high neuroticism scores would mean that a person might be often worried, high-strung, emotional, sensitive, and nervous.

Sample questions:

• I get irritated easily.

• I have frequent mood swings.

• I get stressed out easily.

• I get upset easily.

• I worry about things.

Extraversion

Low extraversion scores tend to be reflective of people who consider themselves as passive, loners, or quiet. They may have lower levels of social engagement, and are more likely to act reservedly in a social setting. High extraversion scores suggests that someone is outgoing, bubbly, talkative, and affectionate. These people tend to get energy from outside settings, and feed off others.

Sample questions:

• I am the life of the party.

• I am comfortable around people.

• I do not mind being the center of attention.

• I start conversations.

• I talk to a lot of different people at parties.

Agreeableness

A low agreeableness score will be seen among people who are irritable, critical of others, and untrusting. High agreeableness would be seen as people who easily get along with each other, demonstrate kindness and consideration towards others, and put the needs of others before oneself.

Sample questions:

• I sympathize with others' feelings.

• I have a soft heart.

• I take time out for others.

• I feel others' emotions.

• I am interested in people.

• I make people feel at ease.

Conscientiousness

A high conscientiousness rating indicates that a person is able to regulate and control their impulses or desires, or that person may be perceived as stubborn or hardheaded. A person with a low conscientiousness score may be flexible or capable of adapting to change, but negative traits associated with low consciousness score may be seen as sloppy or unreliable.

Sample questions:

• I like order.

• I follow a schedule.

• I am always prepared.

• I always pay attention to details.

• I get chores done right away.

• I am exacting in my work.

Openness to experience

High openness may be reflective of a person’s appreciation for art or adventure. These people tend to be more creative and more aware of their feelings. A low openness score may indicate that a person may be driven by dogma or more closed-minded in general.

Sample questions:

• I have excellent ideas.

• I am quick to understand things.

• I use difficult words.

• I am full of ideas.

Examples of academic studies on the Big Five Personality Traits

People’s scores on these behavioral tests tend to be sensitive to changes in age, a phenomenon called maturation effect. In general, as a person moves from early to late adulthood, they score less on neuroticism and higher on conscientiousness and agreeability. Many analyses of longitudinal data, which correlate people's test scores over time show a high degree of consistency in personality traits during adulthood, especially in the neuroticism trait, which is sometimes regarded as a temperament trait.

Compared to men, women appeared to be score somewhat higher on neuroticism, extraversion, agreeableness, and conscientiousness scores, according to a survey of gender disparities in 55 nations using this Big Five Inventory. Neuroticism was the most noticeable and clear variation, and major variations were observed in 49 of the 55 countries studied. In more prosperous societies, gender variations in personality characteristics are more pronounced. The extent of sex variations between more and less developed world regions was attributed to differences between men, not women, in both of these regions. That is, relative to men in less developed world regions, men in highly developed world regions were less neurotic, extraverted, attentive, and agreeable. (Why can't a man be more like a woman? Sex differences in Big Five personality traits across 55 cultures)

In comparison to laterborns, American psychologist Frank Sulloway argues that firstborns tend to score higher on conscientiousness and lower on openness to new ideas. However, large-scale experiments using random samples and self-report personality tests have shown weaker to no substantial effects of birth order on personality than Sulloway believed. 

According to a new survey of Israeli high-school students, participants in the gifted program ranked higher on openness and lower on neuroticism than those who were not in the gifted program. Though not a Big Five metric, gifted students have showed lower levels of state anxiety than non-gifted students. In addition to academic performance, basic Big Five personality traits predict learning styles. (Do academically gifted and nongifted students differ on the Big-Five and adaptive status? Some recent data and conclusions)

• High scores of conscientiousness predict high GPA and performance on exams

• Academic success is related to low neuroticism 

• High scores on both the openness and extraversion measures both predict a variety of learning styles.

This personality test has also been used in political science research. The major five personality characteristics and political identity have been linked in studies. Several surveys have discovered that people who rank high on conscientiousness are more likely to identify as right-wing politically. On the other hand, people with high scores on openness to experience are likely to identify as left-wing. As far as other measures go, the research is mixed.

Comprehension check: Test yourself on the Big Five Personality Traits

Question 1. Which of the following is not one of the Big Five Personality Dimensions?

A. Openness to experiences
B. Friendliness
C. Neuroticism
D. Consciensciousness
E. Agreeableness

Question 2. How is the Big Five Personality Test scored?

A. Clinician observation
B. Rated by experts after an interview
C. Self report
D. Interviews with those closest to the participant

Often times, people confuse the words epilepsy and seizure. They may mistakenly use the two interchangeably, but they are very different things. To accurately describe a patient, it is critical to know which to use and when.

Epilepsy is a chronic neurological disorder. People with epilepsy experience recurrent seizures, which vary in type and severity. The cause of epilepsy is complex, and many forms of epilepsy are a result of genetics. These genetic changes lead to a dysregulation of the electrical properties of neurons. 

For example, some forms of epilepsy are due to genetic mutations in the voltage-gated sodium channel protein. In these mutations, the channels are more likely to remain active instead of inactivating periodically, as healthy channels do.

Seizures, on the other hand, are the main symptom of epilepsy. In a seizure, unusual electrical activity of neurons lead to muscle spasms, a temporary loss of consciousness, and unusual behavior. There are many different categories of seizures, with generalized vs. partial seizures being the main types.

In people with epilepsy, treatment is mostly with anti-epileptic medications. Many of these drugs dampen overall brain activity, which helps limit the excessive firing that produces the seizure symptoms. However, some of these drugs interfere with other cognitive processes, including memory formation.

Causes of seizures without epilepsy

The difference between epilepsy and a seizure is important because people may have seizures without the diagnosis of epilepsy. These are called acute symptomatic seizures. When non-epilepsy conditions cause seizures, treatment requires a different approach.

In people with severe alcohol use disorder, a sudden withdrawal can lead to a seizure.It is theorized that chronic exposure to alcohol causes a cellular level tolerance to happen, resulting in upregulation of excitatory glutamate receptors. When alcohol is no longer present to decrease excitation, the brain circuits fire too much, which may lead to seizures. Because of this risk, it is important that people with alcohol use disorder do not quit cold turkey, but rather taper off their exposure.  Alcohol withdrawal seizures may be treated with benzodiazepine drugs (including lorazepam and alprazolam), which mimic alcohol’s effect on the cellular level. 

Brain tumors are known to cause seizures. In these cases, clinical brain imaging tools such as a CT scan, MRI, or EEG may reveal the location of the tumor. From there, treatment of the tumor may be surgery, targeted radiation, or chemotherapy.

A sudden blow to the head resulting in traumatic brain injury (TBI) or concussion can result in seizures. In these cases, diagnostic imaging may also be helpful, but they may not be able to detect anything relevant. Henry Molaison, one of the most famous case studies in neuroscience, may have developed his debilitating seizures after an injury sustained during a bicycle accident. 

An infection of the brain, such as neurocyticersosis, can also cause seizures. This is a rare condition where an infection with the parasitic tapeworm Taenia solium forms cysts in the brain. The tapeworm comes from raw pork and poor sanitation conditions. Treatment for this condition involves anti-helminthic drugs, which are drugs such as praziquantel (PZQ), which helps destroy the tapeworm.

Other short-term conditions, ranging from excessive fever, dangerously low blood sugar, and hyponatremia (electrolyte imbalance, typically from drinking excessive amounts of water) can cause seizures. 

In all of these examples of acquired seizures, treatment is best by figuring out the underlying cause. Treatment is best done under the support from health care professionals. Therefore, it is always a good idea to visit a neurologist as soon as you have a first time seizure.

When dissecting the nervous system outside of the brain, it is common to come across large clumps of neuronal cell bodies (also called soma). These clumps are called ganglia (the singular form is ganglion).

Ganglia are a part of the peripheral nervous system, or the PNS. The PNS is divided into three branches. The somatic peripheral nervous system is responsible for communicating to and receiving signals from the surroundings. There are sensory ganglia, such as the dorsal root ganglion. On a microscopic level, the dorsal root ganglion contains the somata of the sensory, or afferent, neurons. These cells are pseudounipolar neurons because they extend their single axon in two different directions: one towards the skin for detecting tactile sensations for example, and the other towards the spinal cord. Historically, these have also been called the spinal ganglion since they are located close to the spinal cord. 

Another component of the peripheral nervous system is the autonomic nervous system, or ANS. The ANS communicates with the internal environment, such as by monitoring the condition of the lungs or stomach. The nerves that communicate to and receive information from these organs often bundle their cell bodies into ganglia as well.

Some of the cranial nerves also have ganglia. Cranial nerves are the 12 pairs of nerves that exit or enter directly from the brain. Many (but not all) are responsible for communicating with the muscles or sensory components of the face, such as the muscles of the eyes or the sensory system that allows for smell. One of the most prominent cranial nerve ganglia is the trigeminal ganglia, which houses the cell bodies of the trigeminal nerve. The trigeminal nerve is important for several functions, including sensing touch information on the skin of the face and controlling the muscles of the jaw and mouth.

Be aware that there are structures in the brain (central nervous system) that are also called ganglia, namely the basal ganglia. The basal ganglia are a series of forebrain structures that are not part of the cortex, and are therefore classified as subcortical. The basal ganglia consists of circuits which connect several brain structures, including the striatum, amygdala, hippocampus, and many others. The basal ganglia is implicated in many different disorders, such as Parkinson’s disease, substance use disorder, and OCD.

In neuroscience research, sometimes scientists develop new techniques to study specific cognitive outcomes. Learning and memory are very important tasks that are important for humans, especially in the context of brain injury or Alzheimer’s disease. It is therefore helpful to invent memory tests using nonhumans, like rats and mice, so that the scientists can more easily test new drugs that might be able to treat amnesia.

The Barnes maze is one such test. This test is a behavioral test, since the rat or mouse is put into the maze, and how they perform is recorded. The maze itself is a large circular platform. At the perimeter of the maze are a number of holes which are spaced evenly apart. Barnes mazes may have between twenty and forty holes. One of these holes has a small tunnel connected to it, which allows the animal to leave the maze. This is the exit. The rat is placed in the middle of the Barnes maze, its position is tracked, and the time it takes to reach the hole containing the tunnel is recorded. 

In terms of the research design, the time spent on the maze is considered to be the dependent variable.

There are also visual cues shown to the animal, which help the animal orient themselves to their surroundings. These are all visible from the center of the maze. Some of these visual cues may include the presentation of different colored shapes, such as posters on the wall.

Memory is a complex cognitive function which has many different forms. The main type of memory being assessed in the Barnes maze is called spatial or navigational memory. Navigational memory is the type of memory that allows the animal to associate a position in space (relative to certain visual cues, for example) with the exit. If the animal has a good spatial navigational memory, they will continue to perform better on the maze (less time spent until exit) the more they practice. 

The Barnes maze takes advantage of a behavior that is intrinsic to small prey mammals like rats and mice. In general, these animals show a natural avoidance to wide open spaces. In the wild, open spaces like a empty grassy field are very risky environments for these animals. Aerial predators, such as hawks or owls, are more capable of spotting their prey if there is no surrounding cover. Naturally, rats and mice will be attracted to spaces that are darker or more enclosed, such as a log or an underground tunnel. 

In terms of the Barnes maze, these natural behaviors are tested. The center of the maze is usually brightly lit, which resembles a grassy field. The escape tunnels are surrounded on all sides, which resembles an underground tunnel. So, the animals prefer to find the tunnel as quickly as possible since it provides the feeling of safety. Therefore, researchers might say that the Barnes maze offers good ethological validity, since it mimics what the animals would seek in the wild.

Many Barnes maze setups are equipped with overhead cameras, which are used to track the path that the animal takes. This provides a little bit more information compared to simply recording time to exit.

The maze is named after Dr. Carol Barnes, who first described her behavioral test in the 1979 publication Memory deficits associated with senescence: A neurophysiological and behavioral study in the rat.

Barnes maze compared to Morris water maze

The Barnes maze is similar to another behavioral test for navigational memory called the Morris water maze. In the Morris water maze, the animal is placed in a swimming pool filled with opaque water. The exit is a platform hidden beneath the surface. Like the Barnes maze, the surroundings contain various visual cues which help the animal form spatial memories. With time and practice, animals start to reach the exit sooner.

The advantage of the Barnes maze is that it is a dry land test. Some experimental paradigms require the use of electronics, such as embedded stimulator probes, cranial window cameras, or tiny electrophysiology rigs. In these experiments, water poses a risk of short circuiting the equipment. However, since the Barnes maze is entirely dry, risk of damage to the electronics is less of a concern.

Another advantage of the Barnes maze is that it doesn’t require the degree of physical fitness that swimming does. The Morris water maze requires that the animal can swim for potential minutes at a time, which may introduce another confounding variable. Walking and exploring the Barnes maze is less demanding, allowing the researcher to focus on the variable of interest, which is spatial navigational learning.

Performance on the Barnes maze and the Morris water maze are dependent on circuits through a brain structure called the hippocampus. Injury to the hippocampus is known to disrupt spatial memory formation. Surgical lesions of the hippocampus reliably impair performance on both of these tasks, causing the rat or mouse to reach the exit slower, even after several trials have been run. 

Barnes Maze protocol

While different research groups will use slightly different protocols, the following is one described in Pitts et al., 2015.

1. The TSE Systems Barnes maze apparatus is a circular white platform with 40 holes equally spaced along the perimeter. One of the holes is designed the escape tunnel. This escape tunnel is not changed.

2. The mouse is placed in the center of the platform for 3 minutes. Time until the animal reaches the exit is recorded. If they do not find the exit, they are placed in the exit for 15 seconds.

3. This was repeated twice a day for a total of 10 days.

4. The data from two different groups were analyzed using a two-way repeated measures ANOVA.

Pitts et al. discovered a decrease in latency (increase in learning) with increased trials. The full text for this protocol can be found here: Competition between the Brain and Testes under Selenium-Compromised Conditions: Insight into Sex Differences in Selenium Metabolism and Risk of Neurodevelopmental Disease.

Source: Barnes Maze Procedure for Spatial Learning and Memory in Mice

The olivary nucleus is an oval shaped prominence in the medulla, a part of the brain stem. The olivary nucleus, or olive, is divided into two parts with two different functions. The superior olive is a part of the pons in the cerebellum, and functions in the auditory pathway. The inferior olive rests below that structure, and functions as a part of the cerebellar motor learning pathway.

Superior olivary complex  (SOC)

When sound waves enter the ear canal, they vibrate the eardrum, in turn causing the ossicles (three tiny bones inside the ear) to vibrate at that same frequency. The vibration is passed into the cochlea, and that structure’s output is sent to the brain via the auditory nerve, a branch of the vestibulocochlear nerve (cranial nerve VIII). This auditory information enters into the superior olive for initial processing before arriving at the auditory cortex.

The superior olivary nucleus can be further divided into the medial and lateral superior olive, which serve slightly different functions in auditory processing. They are both paired structures, meaning on exists on each half of the spinal cord. Collectively, the medial and lateral superior olive serve to help the person identify which direction an auditory stimulus is coming from, the left or the right side of the head.

The medial superior olive functions to determine if a sound is coming from the left or right side of the head by calculating a difference in time from when the sound reaches one ear to the other. Using these data, the medial superior olive can calculate an angle for where a sound has originated. For example, sound waves travel at approximately 300 meters per second. The average width of a human head is about 6 inches. Using these numbers, it can be calculated that a sound wave that originates exactly from the left or right side of the head will reach one ear 700 microseconds before it reaches the other ear.

The lateral superior olive also functions to help identify the origin of a sound. Instead of using temporal differences to make determine the origin of the sound, it uses slight changes in volume. A sound originating on the left side will be louder in the left ear, and when that sound reaches the right ear, that sound wave will be slightly dampened because of the head. The structure receives excitatory inputs from the ipsilateral ear while receiving simultaneous inhibitory inputs from the contralateral ear (The right lateral superior olive gets excitation from the right ear and inhibition from the left ear.)

Inferior olivary complex (IOC)

The inferior olive is located close to the cerebellum and functions as a relay between the spinal cord and cerebellum. Injury to the cerebellum almost always results in inferior olive injury, and inferior olive injury likewise results in cerebellar injury. Such lesions lead to a difficulty with learning complex coordination tasks.

Some disorders affect the inferior olive and cerebellum along with other brain structures. For instance, progressive supranuclear palsy is a disease associated with a problem in the Tau protein that normally functions to maintain the microtubule structure of cells. In this progressive supranuclear palsy, a person experiences bradykinesia (slowed movements) and difficulty with gait and posture during locomotion. Sometimes, they may also exhibit psychological symptoms such as dementia or difficulty with speech. Because the symptoms may appear similar to other neurodegenerative disorders such as Parkinson’s disease or Alzheimer’s disease, progressive supranuclear palsy may be underdiagnosed.

It also is involved heavily in signaling of the spino-olivary tract, which carries information about proprioception from the muscles up the spinal cord. This pathway is sometimes also called Helwig’s tract.

Another important feature of the inferior olivary nucleus is related to the production of sex hormones in the body. For example, the inferior olive produces the enzyme aromatase, which is the primary enzyme that converts testosterone into estradiol.

On the level of neural circuitry, the inferior olive receives GABA-ergic projections from various other structures, including the deep cerebellar nuclei and the parasolitary nucleus (Adaptive Balance in Posterior Cerebellum).

Hallucinations, broadly speaking, are false sensations or perceptions. When people think of hallucinations, they commonly think about auditory hallucinations, such as when a patient hears voices in their head, or visual hallucinations, such as seeing things that aren’t there. Charles Bonnet syndrome, which may happen when a person completely loses their vision and afterwards begins to see vivid imagery, is an example of a visual hallucination disorder.

A less well-known category of hallucinations are somatic hallucinations. These are false sensations or perceptions on your skin, for example, which are called tactile hallucinations. Tactile hallucinations can also affect the joints and muscles. They may feel like something is touching or different temperatures. Sometimes these sensations are also called tactile delusion. Odds are you may have experienced a common somatic hallucination: the phantom phone vibrating in your pocket. 

A different form of a somatic delusion is when we experience some kind of sensation of the internal organs, called visceral hallucinations. These are classified as cenesthetic hallucinations, or cenestopathy. Some sensations reported that qualify as a cenesthetic hallucination include the feeling that the internal organs have shifted around, that there are temperature waves flowing through the internal organs, that the mouth has been coated in slime (called oral cenesthetic hallucinations) or that a part of the body may feel hollow.

What causes cenesthetic hallucinations?

The exact cause of these phantom experiences is unknown. But, some case studies and retrospective studies have provided clues as to what might cause the sensation.

Schizophrenia. Schizophrenia is a mental disorder that affects around 1% of people. It is best known for producing auditory hallucinations and delusional thought, but can also produce cenesthetic hallucinations. In a small study, it was found that upwards of 80% of people with schizophrenia reported some degree of cenestopathy. Some of these patients reported that their body was distorted in size. Since the dopaminergic system is implicated in schizophrenia, there is a suggestion that dopamine dysregulation may be a contributing factor to cenesthetic hallucinations. However, cenesthetic schizophrenia has not been defined as a form of schizophrenia under the Diagnostic and Statistical Manual for Mental Diseases.  

Treatment of Parkinson’s disease with dopaminergic modifying drugs. One of the most common and effective treatments for the motor symptoms of Parkinson’s disease is a levodopa / carbidopa mix. In one case study, a woman reported that she felt as if her bowels had started to extrude from her arms. She felt these sensations so severely that she scratched her arms until lesions formed. Her medical team treated her with a drug called clozapine, which is commonly prescribed as an antipsychotic used for decreasing symptoms of schizophrenia. Clozapine's main mechanism of action is to interact with the serotonin and dopamine systems. 

Stroke recovery. In a rare case study of a stroke survivor, a woman reported the feeling of a metal object in her mouth, characteristics of an oral cenesthetic delusion. Using a real time imaging technique called magnetoencephalography, the researchers believe there was some cortical remapping or restructuring after the stroke that led to expansion of the primary somatosensory cortex. This type of plasticity is seen after many different forms of brain damage. 

How are cenesthestic hallucinations treated?

Generally, cenesthetic delusions are best treated by addressing the underlying cause. Most commonly, this is treating the schizophrenia, which produces both delusional thinking and hallucinations. Schizophrenia symptoms may be treated with some dopaminergic drugs. Drugs used for treating psychosis are often helpful for people with schizophrenia, such as haloperidol (Haldol).

Antidepressants may also have a benefit for these hallucinations. 

Outside of pharmacology, electroconvulsive therapy (ECT) and psychotherapy have been used, with varying results.

The anterolateral system refers to a set of neurons that send signals towards the brain. These neurons carry information regarding temperature and pain, but also crude touch. Activity at this pathway often has a salient motivational component, since painful stimuli or temperature information encourages an action - get away from the painful stimuli or the hot object. Additionally, the brain needs to learn to avoid these potentially damaging stimuli.

The first order sensory neurons have their receptors in the skin, and the cell bodies in the dorsal root ganglion. These cells project into the spinal cord, where they can ascend or descend one or two segments via the posterolateral tract (also called Lissauer’s tract). Then, these neurons synapse onto the second order neurons in the substantia gelatinosa or the nucleus proprius. These cells send their axons across the midline to the other half of the spinal cord, which is the process of decussation. Then, these second order neurons ascend towards the brain, where they synapse onto the third order neurons in the rostral ventromedial medulla. This incoming pain and temperature information then gets passed to the thalamus before eventual processing in the cortex.

At the level of the skin, the first order neurons are sensitive to crude touch, temperature, and pain.

Crude touch information is usually not able to be identified very well. It is produced when an object is in contact with the skin. The two point discrimination for crude touch is very large. Compare this with fine touch, which can identify textures and dots very close together (as in Braille).

The sensation of pain is detected by free nerve endings. A painful stimulus activates specialized receptor cells called nociceptors. Painful stimuli signal to the brain that tissue damage may occur if the muscles are not moved away from the offending stimulus.

Temperature information is also detected by free nerve endings. The receptors that respond to temperature are called thermoreceptors. Cold information is sent to the brain via two types of nerve fibers, the slower C-fibers as well as the faster A delta fibers. A delta fibers transmit information faster because they are myelinated.

In the laboratory, there are many ways to measure pain. One such test, called the von Frey fibers test, is a measure of mechanical pain. To perform this test, a series of carbon fiber probes of different thickness are pressed into the skin. If a person senses pain when a weak probe is pushed into the skin, they may have hyperalgesia, which is a high sensitivity to pain. The pain information carried by a von Frey fiber test ascends towards the brain using the anterolateral system.

The anterolateral system is also called the ventrolateral system or the spinothalamic tract.

Compare this somatosensation pathway with the dorsal column-medial lemniscus pathway, which sends fine touch, vibration, and proprioception information into the brain. Whereas the dorsal column-medial lemniscus pathway decussates at the level of the brain, the anterolateral system decussates at the level of the spinal cord. This means that an injury to one lateral half of the spinal cord may result in a loss of fine touch or vibration information from the same side of the injury (ipsilateral) with a loss of pain or temperature sensation from the side opposite the injury (contralateral). This is referred to as Brown-Sequard syndrome.

Serious games have been created for teaching nearly every academic discipline, ranging from astronomy to microbiology. Here, we present our list of top board and card games that can be used for learning some aspect of neuroscience. Many of them have been adopted by professors and teachers for use in their classrooms. Some even have free versions that are downloadable, which the board game community calls Print and Play, or PnP.

Many of these neuroscience themed serious games are popular, receiving awards for a large number of sales. In no particular order, here are some of BrainStuff.org’s favorite board games.

Foramina

Focus: Neuroanatomy

Designer: Zach London, MD, and Mikaela Stiver, PhD.

Foramina are the holes in the skull which allow bundles of axons, or nerve fibers, to pass into and out of the brain. Foramina is also a set collection game designed to teach about the cranial nerves.

Foramina doesn’t require any previous knowledge about cranial nerve anatomy, so it is perfect for use in an undergraduate level sensory neuroscience or neuroanatomy lab class.

NeuroNavigator

Focus: Neuroanatomy

Designer: Austin Lim, PhD

NeuroNavigator is a competitive board game that asks “Do you know your neuroanatomy?”

In NeuroNavigator, players compete to move around a series of coronal brain slices trying to get to the brain structure identified on cards. First player to reach that structure gets to claim the corresponding number of points.

NeuroNavigator requires an understanding of brain anatomy before play. A free-to-download rulebook provides answers as well as other educational information. The game can be adopted in the classroom to teach how to use the Allen Brain Atlas to find brain structures.

Signal

Focus: Cellular Neuroscience

Designer: Angel Kaur, PhD

In Signal, players look to build a functioning synapse that allows the two neurons to communicate.

Signal has a strong focus on the foundations of cellular and molecular neurobiology, requiring that the students understand the role of such important proteins as voltage gated sodium channels and the sodium-potassium ATP-ase. Using this knowledge, they will compete against other groups to build a working synapse! Signal is ideal for both introductory level neuroscience courses as well as upper level courses.

The use of Signal in the classroom has been described in a publication in the Journal of Undergraduate Neuroscience Education.

Forbidden Neurds

Focus: General neuroscience

Designer: Angel Kaur, PhD

Like Taboo for Neuroscientists, Forbidden Neurds is a group party game designed to test a knowledge of neuroscience words. One player is given a neuroscience-themed word, and the other teammates are tasked with guessing the word. However, the clue giver is forbidden from saying a list of words, so they are going to have to get creative!

Great for use in the classroom, since it challenges students to find new ways to communicate ideas they have previously learned about. Although the rules suggest a time limit, professors could give these cards and ask the students to come up with other words they would use to describe the target word. This “low pressure” mode of game play can also be adopted for a slow paced version of the game.

Are you a designer of a neuroscience themed board game?

We may have missed your game! Please drop a comment below and we will definitely take a look at your game.

Both ethanol (alcohol) and cocaine are addictive substances that are commonly used. Alcohol and cocaine misuse both contribute to tremendous drug related costs, which include harms to both the individual and to society.

Both alcohol and cocaine are broken down after ingestion by enzymes in the liver. In particular, alcohol is degraded by alcohol dehydrogenase into acetaldehyde. Cocaine, on the other hand, is mostly broken down spontaneously by hydrolysis and esterase activity into the inert substance benzoylecgonine - but a small fraction of the cocaine in the body is converted by cytochrome P450s in the liver into norcocaine.

When both drugs are in the system at the same time during use of alcohol and cocaine, a different substance is produced as a result of metabolic breakdown of the two drugs. This substance is called cocaethylene. It is estimated that half life of cocaethylene is between 2 and 3 hours, much longer than that of cocaine. Additionally, the presence of cocaethylene can be detected in urine tests much longer than cocaine alone.

When cocaine alone is in the system, it undergoes hydrolysis due to carboxylase enzymes. When ethanol is present however, a transesterification chemical reaction happens to the cocaine byproduct benzoylecgonine, which results in cocaethylene being formed. (Cocaethylene metabolism and interaction with cocaine and ethanol: role of carboxylesterases)

Pharmacology of cocaethylene

Cocaethylene itself is considered an addictive drug. It’s pharmacological properties include inhibition of the reuptake proteins of three neurotransmitters: norepinephrine, dopamine, and serotonin. In this way, cocaethylene continues the pharmacological manipulation of these neurotransmitter systems as cocaine did, with a longer acting time course.

Self administration of a substance is a useful experimental technique to assess the rewarding properties of a substance. In self administration, it is possible to train an animal to perform some operant task such as lever pressing or nose poking to receive a direct infusion of a drug. It has been demonstrated that monkeys will lever press for intravenous infusions of cocaethylene (Cocaethylene: A neuropharmacologically active metabolite associated with concurrent cocaine-ethanol ingestion). This indicates that cocaethylene is inherently a rewarding substance.

Learning disorders are brain disorders characterized by difficulty with processing some aspect of academic study, such as math, reading comprehension, or writing. Learning disorders are lifelong challenges, and are not necessarily a result of low IQ. The best known learning disability is dyslexia, a difficulty with processing the written word.

Dyscalculia (pronounced “dis-kal-KYU-lee-uh” with the emphasis on the third syllable) is a learning disorder that impairs a person’s mathematical or numerical processing ability. It may be called mathematical learning difficulty, or MLD. It can affect people with a neurotypical range of intelligence. Dyscalculia is common, affecting an estimated 6% of the population. But, it is very difficult to diagnose, meaning this number may be under reported. 

What are the symptoms of dyscalculia?

People with dyscalculia begin showing signs in early childhood, although it persists as an adult. One initial difficulty that may help in diagnosis is a challenge in subitizing, which is the process of quickly determining the number of items there are in a clump without counting them individually.

They also have difficulty learning many of the number related tasks in early education, including determining which number is larger, reading analog clocks, or sorting numbers in ascending order. People with dyscalculia also may learn to perform these tasks one day, but have difficulty remembering how to accomplish the task on the next day.

Dyscalculia is often seen in conjunction with other learning disabilities or conditions. For one, the most common condition that is seen alongside dyscalculia is dyslexia, a similar language-related learning disorder (Developmental dyscalculia and basic numerical capacities: a study of 8–9-year-old students). Dyscalculia is often comorbid with ADHD, and one estimate suggests that 11% of patients with dyscalculia also have ADHD.

Although there is not a universally accepted test for dyscalculia, there are diagnostic tools that may help. One is called the Fundamental Calculative Ability Test (or FCAT), which, when given during the first grade, may help predict mathematical achievement. Low scores on the FCAT may suggest dyscalculia.

One reason why the disorder is so difficult to identify is because of its high comorbidity with dyslexia. Many assessments of mathematical ability require reading ability. To overcome this challenge, a group of researchers published a novel test that may be able to separate mathematical from reading ability (Taking Language out of the Equation: The Assessment of Basic Math Competence Without Language)

What is the cause of dyscalculia?

It is currently unclear what causes dyscalculia. It is believed to be a result of some neural circuitry disruption of the intraparietal sulcus (Impaired neural networks for approximate calculation in dyscalculic children: a functional MRI study). Some of the functions of the intraparietal sulcus include helping an organism with perceptual-motor coordination, such as reaching and grasping for an object. One theory suggests that these areas are also important for the internalization of numbers, such as when a person is counting the number of objects around them. Also, the intraparietal sulcus is important for learning sequences of finger movements (Learning of sequences of finger movements and timing: Frontal lobe and action-oriented representation). Because we most often begin learning mathematical skills by using our fingers, abnormal development of this area believed to correlate with difficulty learning mathematical concepts.

There is also reason to believe that dyscalculia is a result of altered circuitry in the frontal lobe. Parts of the frontal lobe are used in behaviors such as the temporary storage of items during short-term memory tasks. Theoretically, these areas may be involved in the storage of a number which may be needed for arithmetic tasks.