 An MRI scan of the human brain Photo by Katie Nesling/Thinkstock Dopamine Is _________?
Is it love? Gambling? Reward? Addiction? By Bethany Brookshire In a brain that people love to describe as “awash with chemicals,” one chemical always seems to stand out. Dopamine: the molecule behind all our most sinful behaviors and secret cravings. Dopamine is love. Dopamine is lust. Dopamine is adultery. Dopamine is motivation. Dopamine is attention. Dopamine is feminism. Dopamine is addiction. My, dopamine’s been busy. Dopamine is the one neurotransmitter that everyone seems to know about. Vaughn Bell once called it the Kim Kardashian of molecules, but I don’t think that’s fair to dopamine. Suffice it to say, dopamine’s big. And every week or so, you’ll see a new article come out all about dopamine. So is dopamine your cupcake addiction? Your gambling? Your alcoholism? Your sex life? The reality is dopamine has something to do with all of these. But it is none of them. Dopamine is a chemical in your body. That’s all. But that doesn’t make it simple. What is dopamine? Dopamine is one of the chemical signals that pass information from one neuron to the next in the tiny spaces between them. When it is released from the first neuron, it floats into the space (the synapse) between the two neurons, and it bumps against receptors for it on the other side that then send a signal down the receiving neuron. That sounds very simple, but when you scale it up from a single pair of neurons to the vast networks in your brain, it quickly becomes complex. The effects of dopamine release depend on where it’s coming from, where the receiving neurons are going and what type of neurons they are, what receptors are binding the dopamine (there are five known types), and what role both the releasing and receiving neurons are playing. And dopamine is busy! It’s involved in many different important pathways. But when most people talk about dopamine, particularly when they talk about motivation, addiction, attention, or lust, they are talking about the dopamine pathway known as the mesolimbic pathway, which starts with cells in the ventral tegmental area, buried deep in the middle of the brain, which send their projections out to places like the nucleus accumbens and the cortex. Increases in dopamine release in the nucleus accumbens occur in response to sex, drugs, and rock and roll. And dopamine signaling in this area is changed during the course of drug addiction. All abused drugs, from alcohol to cocaine to heroin, increase dopamine in this area in one way or another, and many people like to describe a spike in dopamine as “motivation” or “pleasure.” But that’s not quite it. Really, dopamine is signaling feedback for predicted rewards. If you, say, have learned to associate a cue (like a crack pipe) with a hit of crack, you will start getting increases in dopamine in the nucleus accumbens in response to the sight of the pipe, as your brain predicts the reward. But if you then don’t get your hit, well, then dopamine can decrease, and that’s not a good feeling. So you’d think that maybe dopamine predicts reward. But again, it gets more complex. For example, dopamine can increase in the nucleus accumbens in people with post-traumatic stress disorder when they are experiencing heightened vigilance and paranoia. So you might say, in this brain area at least, dopamine isn’t addiction or reward or fear. Instead, it’s what we call salience. Salience is more than attention: It’s a sign of something that needs to be paid attention to, something that stands out. This may be part of the mesolimbic role in attention deficit hyperactivity disorder and also a part of its role in addiction. But dopamine itself? It’s not salience. It has far more roles in the brain to play. For example, dopamine plays a big role in starting movement, and the destruction of dopamine neurons in an area of the brain called the substantia nigra is what produces the symptoms of Parkinson’s disease. Dopamine also plays an important role as a hormone, inhibiting prolactin to stop the release of breast milk. Back in the mesolimbic pathway, dopamine can play a role in psychosis, and many antipsychotics for treatment of schizophrenia target dopamine. Dopamine is involved in the frontal cortex in executive functions like attention. In the rest of the body, dopamine is involved in nausea, in kidney function, and in heart function. With all of these wonderful, interesting things that dopamine does, it gets my goat to see dopamine simplified to things like “attention” or “addiction.” After all, it’s so easy to say “dopamine is X” and call it a day. It’s comforting. You feel like you know the truth at some fundamental biological level, and that’s that. And there are always enough studies out there showing the role of dopamine in X to leave you convinced. But simplifying dopamine, or any chemical in the brain, down to a single action or result gives people a false picture of what it is and what it does. If you think that dopamine is motivation, then more must be better, right? Not necessarily! Because if dopamine is also “pleasure” or “high,” then too much is far too much of a good thing. If you think of dopamine as only being about pleasure or only being about attention, you’ll end up with a false idea of some of the problems involving dopamine, like drug addiction or attention deficit hyperactivity disorder, and you’ll end up with false ideas of how to fix them. The other reason I don’t like the “dopamine is” craze is because the simplification takes away the wonder of dopamine. If you believe “dopamine is,” then you’d think that we’ve got it all figured out. You begin to wonder why we haven’t solved this addiction problem yet. Complexity means that the diseases associated with dopamine (or with any other chemical or part of the brain, for that matter) are often difficult to understand and even more difficult to treat. By emphasizing dopamine’s complexity, it might feel like I’m taking away some of the glamour, the sexiness, of dopamine. But I don’t think so. The complexity of how a neurotransmitter behaves is what makes it wonderful. The simplicity of a single molecule and its receptors is what makes dopamine so flexible and what allows the resulting systems to be so complex. And it’s not just dopamine. While dopamine has just five receptor type, another neurotransmitter, serotonin, has 14 currently known and even more that are thought to exist. Other neurotransmitters have receptors with different subtypes, all expressed in different places, and where each combination can produce a different result. There are many types of neurons, and they make billions and billions of connections. And all of this so you can walk, talk, eat, fall in love, get married, get divorced, get addicted to cocaine, and come out on top of your addiction some day. When you think of the sheer number of connections required simply for you to read and understand this sentence—from eyes to brain, to processing, to understanding, to movement as your fingers scroll down the page—you begin to feel a sense of awe. Our brain does all this, even while it makes us think about pepperoni pizza and what that text your crush sent really means. Complexity makes the brain the fascinating and mind-boggling thing that it is. So dopamine has to do with addiction, whether to cupcakes or cocaine. It has to do with lust and love. It has to do with milk. It has to do with movement, motivation, attention, psychosis. Dopamine plays a role in all of these. But it is none of them, and we shouldn’t want it to be. Its complexity is what makes it great. It shows us what, with a single molecule, the brain can do. Bethany Brookshire recently completed a postdoc in behavioral neuroscience at the University of Pennsylvania School of Medicine. She blogs for Scientific American at The Scicurious Brain and for Scientopia at Neurotic Physiology. You can follow her on Twitter at @scicurious.  What Causes Essential Tremor? The true cause of essential tremor is still not understood, but it is thought that the abnormal electrical brain activity that causes tremor is processed through the thalamus. The thalamus is a structure deep in the brain that coordinates and controls muscle activity. Genetics is responsible for causing ET in half of all people with the condition. A child born to a parent with ET will have up to a 50% chance of inheriting the responsible gene, but may never actually experience symptoms. Although ET is more common in the elderly -- and symptoms become more pronounced with age -- it is not a part of the natural aging process. Essential tremor is known to be familial condition, meaning that it runs in families. At least 5-7 out of 10 people with essential tremor have other members of the family with the same condition. Genes are passed on to a child from each parent and determine what we look like, how our body functions and even what diseases we get. Particular genes have been shown to have certain changes present in families with essential tremor. It is not clearly understood how this genetic change leads to essential tremor. However, it is likely that it somehow affects some parts of the brain that are responsible for controlling movement. What is tremor? Tremor is an unintentional, rhythmic muscle movement involving to-and-fro movements (oscillations) of one or more parts of the body. It is the most common of all involuntary movements and can affect the hands, arms, head, face, voice, trunk, and legs. Most tremors occur in the hands. In some people, tremor is a symptom of a neurological disorder or appears as a side effect of certain drugs. The most common form of tremor, however, occurs in otherwise largely healthy people. Although tremor is not life-threatening, it can be embarrassing to some people and make it harder to perform daily tasks. What are the characteristics of tremor? Characteristics may include a rhythmic shaking in the hands, arms, head, legs, or trunk; shaky voice; difficulty writing or drawing; or problems holding and controlling utensils, such as a fork. Some tremors may be triggered by or become exaggerated during times of stress or strong emotion, when the individual is physically exhausted, or during certain postures or movements. Tremor may occur at any age but is most common in middle-aged and older persons. It may be occasional, temporary, or occur intermittently. Tremor affects men and women equally. A useful way to understand and describe tremors is to define them according to the following types. Resting tremoroccurs when the muscle is relaxed, such as when the hands are lying on the lap or hanging next to the trunk while standing or walking. It may be seen as a shaking of the limb, even when the person is at rest. Often, the tremor affects only the hand or fingers. This type of tremor is often seen in patients with Parkinson’s disease. An action tremor occurs during any type of movement of an affected body part. There are several subclassifications of action tremor. Postural tremor occurs when the person maintains a position against gravity, such as holding the arms outstretched. Kinetictremor appears during movement of a body part, such as moving the wrists up and down, while intention tremor is present during a purposeful movement toward a target, such as touching a finger to one’s nose during a medical exam. Task-specific tremor appears when performing highly skilled, goal-oriented tasks such as handwriting or speaking. Isometric tremor occurs during a voluntary muscle contraction that is not accompanied by any movement. How common is essential tremor?
Essential tremor is a common disorder, affecting up to 10 million people in the United States. Estimates of its prevalence vary widely because several other disorders, as well as other factors such as certain medications, can result in similar tremors. In addition, mild cases are often not brought to medical attention, or may not be detected in clinical exams that do not include the particular circumstances in which an individual's tremor occurs. Severe cases are often misdiagnosed as Parkinson disease. What genes are related to essential tremor?The causes of essential tremor are unknown. Researchers are studying several areas (loci) on particular chromosomes that may be linked to essential tremor, but no specific genetic associations have been confirmed. Several genes as well as environmental factors likely help determine an individual's risk of developing this complex condition. The specific changes in the nervous system that account for the signs and symptoms of essential tremor are unknown. What is Essential Tremor Essential tremor is when you have uncontrolled shaking movements in parts of your body - most commonly the arms and hands. It is more common with increasing age. It tends to occur in families. It is mild in some people but can become severe and disruptive to daily activities in others. There is good treatment available in the form of medication and occasionally surgery. What is tremor?A tremor is a repetitive movement of a part of the body. It is involuntary. This means that it is generally not controllable and happens without you deciding to move that body part. It is often felt as a trembling or shaking sensation. A slight tremor is present in all people. That is called physiological tremor. It may not be noticeable. Certain things will make a physiological tremor more noticeable such as caffeine (in coffee, tea and cola), anxiety or tiredness. What is essential tremor? Essential tremor is also called familial essential tremor. It is different from physiological tremor described above. It usually starts in the hands and arms. It can sometimes become quite severe so that everyday activities like holding a cup can be difficult. The tremor is usually not there at rest but becomes noticeable when the affected body part is held in a position, or with movement. The term 'essential' means that there is no associated disease that causes the tremor. What causes essential tremor? Essential tremor is known to be familial condition, meaning that it runs in families. At least 5-7 out of 10 people with essential tremor have other members of the family with the same condition. Genes are passed on to a child from each parent and determine what we look like, how our body functions and even what diseases we get. Particular genes have been shown to have certain changes present in families with essential tremor. It is not clearly understood how this genetic change leads to essential tremor. However, it is likely that it somehow affects some parts of the brain that are responsible for controlling movement. Who has essential tremor? Studies have shown different rates of essential tremor. Some have shown it to be present in 3 in 1,000 people, whereas other studies have shown it may affect as many as 5 in 100 people. It is equally common in men and women and is more common with increasing age. Most people who develop essential tremor are aged over 35, but it can occur in younger people. What are the symptoms? The only symptom in essential tremor is tremor. If you have other symptoms, then you may have a different condition. (For example, tremor can be a symptom of various conditions such as Parkinson's disease. In these other conditions, tremor is just one of several other symptoms.) In essential tremor, the tremor usually begins in one arm or hand. Within 1-2 years, the other arm is likely to be affected. Very occasionally, it may also spread to involve the legs. Three in ten people with essential tremor have a tremor of the head. The voice, jaw or face may also be involved. At first, the tremor may not be present all the time. Eventually it will be present all the time when the affected body part is held in a position or with certain movements. It may be worse with stress, tiredness, hunger or certain emotions such as anger. Extremes in temperature may also make the tremor more severe. You may be able to control the tremor to an extent. It may be less noticeable when you are working with the affected body part. For example, when you use your hand the tremor may ease off. It is not present when you are resting or sleeping. Up to 7 in 10 people with essential tremor find that the tremor reduces after drinking some alcohol. How is essential tremor diagnosed? There is no test to diagnose essential tremor. Your doctor can usually diagnose essential tremor based on your explanation of the tremor and an examination. It is important for the doctor to make sure that there are no other conditions present that are causing tremor. In some cases, this may mean that you need to have some tests to rule out other conditions. For example, blood tests or a brain scan. You may also be referred to a neurologist (a doctor with a special interest and expertise in the brain and nerves). While the diagnosis of ET remains a visual one, certain brain scans Magnetic Resonance Imaging (MRI) and Computerized Tomography (CT) may be helpful in eliminating any other conditions which also produce tremor as a symptom. For example growths such as tumours or damage to the brain can be seen on certain brain scans. Blood samples may also be taken to rule out thyroid or copper metabolism problems, both of which can cause tremor. DATScan a diagnostic test can distinguish between ET and tremors of Parkinson's disease. Other conditions that can cause tremor and need to be ruled out include: a side-effect from some prescribed medicines, anxiety, caffeine, some poisons, kidney and liver disease, thyroid disease, Parkinson's disease and other movement disorders. What is the treatment for essential tremor?Essential tremor cannot be cured. Treatment reduces the severity of the tremor, sometimes greatly. There are various treatments that are used. No treatment is an option If your tremor is mild, you may not need any treatment. Medication There are two medicines used initially for essential tremor - propranolol and primidone. These medicines have been shown to ease the tremor in up to 8 in 10 affected people. Propranolol - this is a medicine that is usually used in heart disease. It is in a class of medicines called beta-blockers. It has also been shown to be effective in essential tremor. This medicine should be used with care if you have a heart conduction problem or a lung disease such as asthma. The most common side-effects with propranolol are dizziness, tiredness and nausea (feeling sick). Primidone - this is a medicine that is primarily used for epilepsy, but it also works very well in essential tremor. The most common side-effects are sleepiness, dizziness and nausea. These may improve if you continue to take this medicine. When the diagnosis of essential tremor is made, you may be offered one of these medicines. A low dose is usually started at first, and gradually increased until your tremor is eased. If you reach the maximum dose without a satisfactory improvement, then the other medicine can be tried. If that also doesn't work, you can try them together. Other medicines can be tried if these two are not effective. A wide range of medicines have been shown to have some effect on reducing the severity of the tremor. Surgery If medicine treatment is not effective, and the tremor is severe, then a surgical procedure may be an option. There are two main surgical procedures that may be considered - thalamotomy and thalamic deep brain stimulation. They both involve the thalamus. This is a deep part of the brain that organises messages travelling between the body and brain.
INSIGHTEC FOR NEUROSURGERYINSIGHTEC provides a non-invasive, image-guided alternative for deep brain procedures such as thalamotomy and pallidotomy for essential tremor, tremor dominant Parkinson’s disease and neuropathic pain. This personalized treatment is done through an intact skull with no ionizing radiation, providing a real impact on patients’ quality of life. MINIMAL HOSPITALIZATION and short recovery timeSHARP, ACCURATE Lesions as small as 2mm, no penetrating trajectories, no implanted hardware, no ionizing radiation, less risk of infection REAL TIME MRI guidance for targeting and thermal feedback, with immediate results INSIGHTEC’s neurosurgery solution, Exablate Neuro, is the first focused ultrasound device approved by the FDA to treat patients with essential tremor. Exablate Neuro is a non-invasive, image-guided personalized thalamotomy, treated through an intact skull that doesn't require any ionizing radiation, incisions or implants. What is Exablate Neuro? High intensity focused ultrasound waves precisely target a focal point in the Vim nucleus of the thalamus, the tiny part of the brain that is thought to be responsible for causing tremors. The Exablate Neuro ultrasound transducer consists of 1024 beams that generate enough heat to ablate the targeted tissue during treatment. The result is an immediate and significant reduction of tremor for patients. During planning and treatment for essential tremor, the patient is fully conscious and lying on the treatment bed in an MRI scanner. MRI provides high resolution visualization, patient-specific treatment planning and continuous monitoring of the procedure. Real-time thermal feedback allows the physician to control and adjust the treatment, ensuring that the targeted tissue is completely ablated without impacting adjacent healthy tissue. This revolutionary, non-invasive treatment offers a life changing treatment to patients with essential tremor. Thalamotomy - in this procedure, the thalamus on one side of the brain is destroyed. It has been shown to be very effective. It stops or greatly reduces the tremor in up to 9 out of 10 people with essential tremor. There are risks involved such as a bleed into the brain. Potential side-effects include muscle weakness, speech problems and memory loss. If the thalamus on both sides of the brain is destroyed, there is a higher chance of side-effects. This is not usually recommended. Thalamic deep brain stimulation - this procedure involves placing an electrode (fine wire) into the thalamus on one or both sides of the brain. The electrode is connected to a device called a stimulator. The electrode and stimulator stay in the body. (The stimulator is placed under the skin at the top of the chest.) The simulator sends electrical impulses down the electrode to the thalamus. It is not known exactly why this device works. It seems to interrupt or block the nerve signals coming through the thalamus that cause the tremor. If you have this procedure, you will need to have regular reviews to make sure that the stimulator setting is correct. This aims to minimise side-effects and maximise benefit. It may produce a good response in up to 9 out of 10 affected people. Again, there is a small risk that the procedure may cause a bleed into the brain. Side-effects include loss of sensation, speech problems and weakness. These usually resolve when the stimulator settings are adjusted. Botulinum toxin injections (Botox®)There is some evidence that Botox® injections are helpful in reducing certain tremors. Unfortunately, a Botox® injection into the arm also produces weakness of the arm. This is usually not tolerated. It is mainly useful when essential tremor affects the head and neck. Alcohol Many people find that alcohol is helpful in reducing their tremor. It needs to be used with caution to avoid developing an alcohol problem. It is not advisable to drink more than the normal recommended amount of alcohol. That is: men should drink no more than 21 units of alcohol per week, no more than four units in any one day, and have at least two alcohol-free days a week. Women should drink no more than 14 units of alcohol per week, no more than three units in any one day, and have at least two alcohol-free days a week. Pregnant women, and women trying to become pregnant, should not drink alcohol at all. One unit is in about half a pint of normal strength beer, or two thirds of a small glass of wine, or one small pub measure of spirits. Intermittent treatment Some people with essential tremor only wish to have treatment for specific times. For example, prior to going to a social engagement or before a particularly important meeting. In these situations a single dose of propranolol or an alcoholic drink may ease the tremor satisfactorily for the occasion. What is the outlook? Essential tremor is called a progressive disease. This means that it tends to gets worse over time. It does not shorten expected lifespan and does not lead on to any more serious brain disorders. Some people have a mild tremor which does not affect daily life very much. If your tremor is more severe, it may significantly disrupt your ability to carry out normal activities such as drinking from a cup. However, treatments work well to ease the severity of the tremor in most people with essential tremor. |
