Disorders & Diseases of the Basal Ganglia (incl. Stroke)

The basal ganglia are implicated in many neurological diseases and disorders, from Parkinson’s disease to insomnia to anxiety & depression. Read on to learn more about what happens when the basal ganglia stop working the way they should.

What Are the Basal Ganglia?

The basal ganglia are a group of specialized brain cells located deep in the middle of the brain. Their most important roles are to orchestrate movement, regulate feelings of reward, and govern other instinctual needs. These are very old functions and concerns on the evolutionary time scale: the basic structure of the basal ganglia has been the same for almost all of vertebrate evolution [1, 2].

The largest structure in the basal ganglia, the striatum (composed of the caudate, putamen, and nucleus accumbens in the image above), receives signals from parts of the brain using dopamine. It then sends out new signals using GABA [1].

To learn more about how the basal ganglia function normally, check out this post.

Health Disorders Linked to Basal Ganglia Issues

If your basal ganglia become dysfunctional — be it from stress, psychological issues, brain damage, or more subtle triggers — many problems can arise. The symptoms and health conditions you may experience as a result depend on several complex factors such as:

• Which part of the basal ganglia is affected
• Whether other parts of the brain are damaged
• If the whole structure or part of it is over- or under-active
• Your age, sex, and genetic predispositions
• Your overall health status

…and many more.

Only a specialized health team, headed by a neurologist, will be able to diagnose any issues with this otherwise elusive group of tissues. Nonetheless, understanding the science behind any dysfunction can be empowering. The purpose of this section is to help you understand this deep-seated brain structure a bit better, not to point to any diagnostic factors!

1) Huntington’s Disease

Huntington’s disease is a hereditary neurodegenerative disorder that usually surfaces in a person’s 30s or 40s. People with Huntington’s disease have problems with movement and usually develop uncontrolled writhing movements called chorea. Other common symptoms include learning difficulties and depression [3].

In Huntington’s, a genetic mutation causes neurons in a region of the basal ganglia called the striatum to die. These are the cells that manage movement: as they are damaged and die off, the affected person loses muscle control [4, 3].

Huntington’s disease is caused by high levels of repetition in the gene that codes for a protein called huntingtin. Researchers have yet to discover exactly why this repetition causes damage to the basal ganglia [5].

2) Parkinson’s Disease

Parkinson’s is another neurodegenerative disease characterized by movement problems. These include shaking and stiffness of the muscles, which leads to slow movements and difficulties with balance, speech, and writing. Sleep disorders, depression, and intellectual difficulties might also arise [6].

A group of basal ganglia cells called the substantia nigra, which means “black substance”, releases dopamine and helps coordinate movement. Their cell bodies are black because of a dark pigment called neuromelanin, which is formed from excess dopamine [7, 8, 9, 10].

In Parkinson’s disease, the immune system attacks these pigmented neurons: this reduces dopamine release. It blocks impulses from other parts of the brain, making the initiation of movement impossible: people with Parkinson’s have trouble beginning a movement. Damage to the basal ganglia explains the hallmark symptoms of Parkinson’s; movement problems first appear when 30 – 70% of cells in the substantia nigra have died [9, 11, 7, 8, 12].

Many people with Parkinson’s disease experience minor illusions that may progress to clear hallucinations. Hallucinations, in turn, can lead to delusional thinking. Damage to the basal ganglia can cause hallucinations and delusions after a stroke; a similar mechanism may be at work in Parkinson’s. These symptoms may also be a result of damage to different brain regions [13, 14, 15].

The exact cause of Parkinson’s is unknown, but some forms of the disease are genetic. One form of genetic Parkinson’s disease, called PARK9 or Kufor-Rakeb syndrome, sometimes presents with unusually high levels of iron in the basal ganglia [11].

3) Basal Ganglia Stroke

When brain cells are completely cut off from their oxygen supply, they can no longer function. After a few minutes, cells start to die: this event is called a stroke or infarction. Stroke can affect many brain regions, including the basal ganglia [16, 17].

Movement Disorders

Stroke affecting the basal ganglia usually causes movement disorders, but the precise type of disorder depends on many factors. The injury’s location, severity, and the person’s age and susceptibility may all combine and interact to determine how movement is affected [18].

Some disorders that may result from a basal ganglia stroke include:

• Chorea: quick, random, involuntary writhing movements of the entire body, but mainly of the feet and hands. Chorea is very common after a stroke. Ballism is closely related to it, but it’s more rare and severe. Movements originate in the upper arm and thigh [18, 19].
• Dystonia: sustained contraction of muscles, often in the hand, foot, face, and tongue. It takes almost 10 months to appear after a stroke and usually fades or disappears with time [18, 20].
• Myoclonus: sudden, irregular bursts of shaking movements similar to that of people with epilepsy [18, 21].
• Tremor: shaking, usually of the hands and arms, but all parts of the body can be affected. It is similar to myoclonus, but more rhythmic [18, 22].
• Complex movement disorders: A combination of symptoms from the more defined movement disorders in this list [18].
• Restless leg syndrome: an uncontrollable need to move the legs, especially at night. This syndrome is described more fully in the section below [23].

Reversal Learning

Reversal learning is a type of impulse control: the ability to resist taking an action that was previously rewarded. Cognitive flexibility, or the ability to adapt to new situations, is a product of reversal learning [24, 25].

People who have suffered a stroke to the basal ganglia often have reversal learning difficulties [17].

4) Restless Leg Syndrome

People with restless leg syndrome, or RLS, are uncomfortable when sitting or lying still and have an uncontrollable need to move their legs. Symptoms are at their worst in the evening and at night, which makes it difficult to fall asleep and stay asleep. Poor sleep quality decreases a person’s ability to function during the day, so RLS affects the daytime quality of life as well [23].

The causes of RLS are not well understood. However, the substantia nigra in the basal ganglia in RLS is altered: it has decreased iron levels and impaired dopamine activity. Furthermore, people who have suffered a stroke in the basal ganglia sometimes develop RLS [23, 18].

5) Tourette Syndrome

A person with Tourette Syndrome has tics: automatic movements, sounds, and words. These tics are technically voluntary, but they are prompted by an involuntary urge that can only be satisfied or reduced by making the tic [26].

Problems with the basal ganglia are likely involved in triggering Tourette. In the brains of people with this syndrome, the basal ganglia are not properly connected to the supplementary motor area, another part of the brain that controls movement [26].

Furthermore, the composition of the basal ganglia is changed in Tourette: certain neurons become more and others less dense, but their overall number decreases. These neurons (containing parvalbumin) stimulate the production of GABA, which normally inhibits movement. Low GABA levels from fewer brain cells in this region may play a role in the development of Tourette Syndrome [26, 27, 28].

Tics are most severe in childhood and almost always improve or disappear in adulthood. About half of children with Tourette Syndrome no longer have tics as adults [26].

6) Meige Syndrome

Meige syndrome is a rare disorder that provokes spasms in the eyelid muscles and uncontrollable muscle contractions in the face, jaw, and tongue. Its causes are not well-studied, but it can develop after exposure to levodopa and antipsychotic drugs that may damage the basal ganglia [29].

7) Wilson’s Disease

Wilson’s disease is another rare disorder that gives rise to movement problems similar to those in Parkinson’s disease. It is caused by a genetic disease defect in a liver protein that processes copper and removes it from the body. In a person with Wilson’s disease, copper builds up in the liver and basal ganglia, resulting in liver failure and difficulties with motor control [30, 31, 32].

8) Anxiety

Essentially, anxiety sets off an exaggerated fear response to threats that may not exist. People with anxiety try to avoid the situations that triggered intense fear in the past (aversive behavior), which may interfere with everyday tasks, like going to work or making an important phone call. About one in four people will suffer from an anxiety disorder in their lives [33, 34, 35].

Dysfunction in the basal ganglia can lead to anxiety disorders. The basal ganglia, among its other functions, normally processes information about rewards: it helps you recognize when something good has happened and how to repeat the experience [36].

The striatum is a part of the basal ganglia which is heavily involved in processing and sensing rewards. This region also organizes stimuli by their importance: it helps you pay attention to the things that are important and ignore the things that are not. In people with anxiety, the striatum may give much higher importance to both real and imaginary threats compared to potential rewards [37, 38].

On the other hand, the striatum also helps avoid threats, fear, and other unpleasant feelings. This response, if overactive, may help explain some aspects of anxiety, such as the avoidance of everyday tasks that can become crippling [37].

From this perspective, the basal ganglia in people with anxiety are making wrong judgement calls, and may be biasing your perception of reality. By judging threats to be more important than rewards, your brain will steer you to less pleasant experiences. By seeking to avoid past threats, your brain may greatly limit the situations that won’t provoke an anxious response.

The striatum and the rest of the basal ganglia change a great deal during adolescence. The fear responses you learned as a teenager are processed differently than those you learned as either a child or an adult. Changes in the basal ganglia during adolescence may be the root of some anxiety disorders. In other cases, anxiety may develop due to inflammation in the basal ganglia [37, 38, 39].

68% of people with anxiety also have another mental illness, which is unsurprising given how many mental health and brain disorders may involve the basal ganglia [40].

9) Mood Disorders

Depression is a surprisingly common mental illness: more than 10% of adults experience a depressive episode at least once in their lives. During these episodes, people go through negative (depressed) mood and lose interest in the things they otherwise enjoyed [40].

Mood disorders, including depression, may develop as a result of inflammation in the basal ganglia. Cytokines, compounds released during chronic inflammation, cause changes in the structure of the basal ganglia. They decrease the production and effectiveness of dopamine, which can cause low mood, fatigue, and other symptoms [39, 41, 42].

In addition to depression, cytokines and inflammation in the basal ganglia can cause or contribute to bipolar disorder, irritability, and seasonal affective disorder [41, 43, 44, 45].

10) Insomnia

Dopamine in the basal ganglia helps regulate sleep. When there isn’t enough dopamine in the basal ganglia, nighttime wakefulness and insomnia – the inability to sleep – can arise. People with other mentioned conditions, especially Parkinson’s disease, often suffer from insomnia for this reason [46].

Weak communication between different parts of the brain may also cause insomnia. In particular, the brains of people with insomnia show weak connectivity between the amygdala and striatum of the basal ganglia [47, 48, 49].

11) ADHD

Attention deficit hyperactivity disorder, or ADHD, causes a variety of symptoms. These span the inability to focus, control impulses, or sit still: the ADHD triad of inattentiveness, impulsivity, and hyperactivity. ADHD is often considered a childhood disorder, but up to 65% of children still have it as adults [50, 51].

The basal ganglia may play a role in ADHD: people with ADHD have a smaller than normal striatum. As a result, they don’t produce enough dopamine. This lack of dopamine probably causes the classic ADHD symptoms triad [50, 52, 53].

12) Autism

Autism is a behavioral disorder with a very wide array of symptoms that range from mild to disabling. 1.68% of eight-year-old children were diagnosed with autism in the USA in 2014. Currently, the rate of autism is about 1% in both children and adults – subject to change depending on how we understand and define this disorder [54, 55, 56].

People with autism have structurally different brains. The striatum of the basal ganglia, in particular, is larger and deformed in autistic brains. These differences may explain why people with autism have difficulty predicting consequences and responding to social cues [56, 57, 58, 59].

13) Schizophrenia

Schizophrenia is a severe mental illness. Symptoms can include illogical thoughts, hallucinations, trouble focusing, motivation difficulties, and problems expressing emotions. Some report an inability to find joy or pleasure, similar to people with depression [60, 61].

The basal ganglia are much less active in the brains of people with schizophrenia than in healthy people. However, people with schizophrenia also appear to produce more dopamine in the striatum. Furthermore, communication between the basal ganglia and other parts of the brain is disrupted in schizophrenic brains [60, 62].

Increases in dopamine above healthy levels probably cause schizophrenic hallucinations. Meanwhile, the overall decrease in basal ganglia activity may explain the lack of focus, motivation, emotional expression, and enjoyment of activities [60].

14) Obsessive Compulsive Disorder

Obsessive-compulsive disorder, or OCD, is a mental health disorder marked by obsessions and compulsions. Obsessions extremely distressing unwanted, repetitive thoughts, images, urges, and fears. People will try to fight them off by taking some compulsive action, which often seems irrational or excessive [63].

Communication between the striatum of the basal ganglia and other parts of the brain is weakened in people with OCD. This miscommunication is similar to that in schizophrenia and depression, which suggests similar underlying problems in the brain [62].

15) Addiction

Substance Abuse

When we think of addiction, we usually think of addictive substances like tobacco, alcohol, heroin, or cocaine. Substance abuse of this type is mediated by a structure in the basal ganglia called the nucleus accumbens, sometimes called the reward center [64, 65, 66].

The nucleus accumbens creates the rewarding feelings that come along with addictive drugs. This region of the basal ganglia is sensitive to dopamine, which, in short, makes you feel good. Drugs like heroin and cocaine massively increase the amount of available dopamine in your brain, stimulating the nucleus accumbens and creating the addictive high. The addiction produced by all this dopamine is so powerful that, in some studies, animals will choose cocaine over food until they starve to death [67, 65].

Over time, the nucleus accumbens becomes less sensitive to this dopamine rush and the pleasant feelings associated with the drug are no longer produced. Instead, the periods in between doses become increasingly uncomfortable and eventually painful. Taking more of the addictive substance becomes the only way to relieve this discomfort [65].

Substance abuse and long-term addiction can have lasting effects on people’s DNA. Cocaine, in particular, affects multiple genes in the nucleus accumbens of the basal ganglia and permanently changes glutamate pathways [67].

Other Addictions

The same neurological mechanisms that get us addicted to substances can also get us addicted to other things, like the internet and pornography [66, 68].

All addictions result from a stimulus, either chemical or otherwise, hijacking the nucleus accumbens and the reward pathways in the brain [66].

Genetics of the Basal Ganglia

Huntington’s Disease

In Huntington’s disease, the protein huntingtin has an unusually long polyglutamine tract: a part of the protein made of only the amino acid glutamine. This long glutamine chain is caused by repetitions of the sequence CAG in the IT-15 gene, also called the HD gene or HTT [5, 69, 70].

Generally speaking, people with over 36 CAG repeats in this gene may develop Huntington’s disease, and people with over 39 CAG repeats are likely to develop Huntington’s disease. The more repeats a person has, the earlier in life they develop the disease. Up to 120 CAG repeats have been observed in a single person’s genome [5].

Parkinson’s Disease

In some people with Parkinson’s, the disease can be explained by mutations in one or more different genes. The names and functions of these genes are in bold below, and individual mutations (and SNPs) follow.

Parkinson’s disease has been associated with the genes [6]:

• SNCA produces alpha-synuclein, a protein in brain cells that may be involved in dopamine release and transport. At least 30 different mutations in SNCA are associated with Parkinson’s disease. These include: A30P (rs104893878), E46K (rs104893875), H50Q (rs201106962), G51D (rs431905511) and A53T (rs104893877) [71].
• LRRK2 produces the leucine-rich repeat kinase 2, which helps transmit signals and turns on and off different cell functions. More than 100 different mutations in LRRK2 are associated with Parkinson’s disease. These include: G2019S (rs34637584), R1441C/G/H (rs33939927, rs33939927, rs34995376), Y1699C (rs35801418), and I2020T (rs35870237) [72, 73].
• PRKN produces parkin, which helps break down and dispose of damaged or unneeded proteins. More than 200 different PRKN mutations are associated with early-onset Parkinson’s disease, including V148E (rs1060502319) [74, 75].
• GBA produces glucosylceramidase beta, another part of the cell’s breakdown machinery. Many mutations at GBA are associated with Parkinson’s disease. These include: K480N (rs1057519356), P426L (rs1057519357), P427L (rs1057519357), and I407T (rs10575358).
• PINK1 produces PTEN-induced kinase 1, which may protect the mitochondria within cells from stress. Dozens of mutations at PINK1 may be associated with Parkinson’s disease. These include: P399L (rs119451946), H271Q (rs28940284), L347P (rs28940285), and Q456* (rs45539432) [76, 77].
• PARK7 produces a protein that protects neurons against stress and cell death. More than 25 mutations of this gene have been associated with Parkinson’s disease. These include: A39S (rs137853051), E163K (rs200968609), and L166P (rs38938172).
• VPS35 (also called PARK17) produces vacuolar protein sorting 35, which transports proteins within cells. The Asp620Asn mutation (rs188286943) of this gene has been strongly associated with adult-onset Parkinson’s disease [78, 79].
• EIF4G1 (also called PARK18) produces the eukaryotic translation initiation factor 4 gamma 1, which is important for making new proteins within cells. The R1205H (rs112176450) and A502V (rs111290936) mutations in this gene are linked to adult-onset Parkinson’s disease [80, 81].
• DNAJC13 (also called PARK21) produces the receptor-mediated endocytosis 8 protein, which helps transport compounds into cells. The N855S (rs387907571) mutation of this gene is associated with late-onset Parkinson’s disease [82, 83].
• CHCHD2 (also called PARK22) produces a protein that helps regulate cell death. Two rare mutations of this gene, T61I (rs864309650) and R145Q (rs752169833), have been associated with Parkinson’s disease [84, 85, 86].

Further Reading

• Basal Ganglia: Definition, Function, Location & Anatomy