00:03The basal ganglia are a group of structures that include the caudate, putamen, globus pallidus,
00:09substantia nigra, and subthalamic nucleus.
00:12The caudate and putamen are often referred to collectively as the striatum.
00:17The substantia nigra consists of two regions, the substantia nigra pars compacta and the
00:23substantia nigra pars reticulata.
00:26And the globus pallidus is divided into the internal and external globus pallidus.
00:33The traditional view of the basal ganglia emphasizes their role in movement, and suggests they
00:37are important to facilitating desired movements and suppressing unwanted ones.
00:42We now know, however, that the movement-related operations of the basal ganglia are more complex,
00:48and also involve tasks such as selecting which action to take to achieve a goal.
00:53Additionally, it is thought that the basal ganglia contribute extensively to non-motor
00:58functions, playing an important part, for example, in learning that depends on feedback
01:02and reinforcement, the development of habits, and a variety of other cognitive, motivational,
01:08and emotional functions.
01:12The basal ganglia are thought to shape behavior through circuits organized in loops, which
01:17carry information from other brain regions into the basal ganglia, and then send process signals
01:22back out to influence activity elsewhere in the brain.
01:26Much of the information the basal ganglia receive comes from the cerebral cortex and travels first
01:31to the striatum, which is a main input area of the basal ganglia.
01:35The main output nuclei of the basal ganglia are the internal globus pallidus and the substantia
01:40nigra pars reticulata, which send projections out of the basal ganglia to the thalamus as
01:46well as to nuclei in the brainstem.
01:49Through its connections in the thalamus, the basal ganglia can communicate with the cerebral
01:53cortex and various other structures.
01:58Importantly, activity in the basal ganglia does not cause movement directly.
02:02Instead, the basal ganglia affect movement by modulating activity in other brain regions,
02:07such as the motor cortex.
02:09One influential model proposes that the basal ganglia contain a circuit called the direct
02:13pathway, which facilitates desired movements, and a circuit called the indirect pathway,
02:18which suppresses undesired movements.
02:22It's important to note, however, that research indicates the basal ganglia are more complex
02:26than the traditional direct and indirect pathway model suggests.
02:31In addition to these circuits, a hyper-direct pathway has been identified, and much of the
02:36intrinsic circuitry of the basal ganglia is still being investigated.
02:40Nevertheless, we will now turn to an explanation of the traditional model involving the direct
02:45and indirect pathways, speaking mostly in the context of movement, before discussing how
02:50the basal ganglia might be involved in non-motor functions.
02:57The direct pathway ultimately influences glutamate neurons that project from the thalamus to motor
03:02regions of the cerebral cortex.
03:05These excitatory projections are thought to be involved with stimulating movement.
03:10Neurons from the globus pallidus internal and substantia nigra pars reticulata, however,
03:14project to the thalamus and maintain a steady release of the neurotransmitter GABA, which
03:19acts to inhibit the thalamic neurons and suppress movement.
03:22This mechanism is thought to be important in keeping unwanted movements from occurring.
03:27When we want to make a movement, however, information about the movement is sent from the cortex
03:32to the striatum via the corticostriatal pathway.
03:35Glutamate neurons in this pathway excite neurons in the striatum, and the activated striatal neurons
03:40release GABA in the globus pallidus internal and substantia nigra pars reticulata, inhibiting
03:46the activity of these regions and stopping the inhibition of neurons in the thalamus that
03:50are involved with movement.
03:52This effectively opens a gate for movement to occur.
03:56Activity along this pathway tends to occur just prior to a movement, and thus has been linked
04:00to the facilitation of movement.
04:03The substantia nigra pars compacta is thought to modulate the activity of the direct pathway.
04:08Neurons from the substantia nigra pars compacta travel to the striatum via the nigrostriatal
04:13pathway and release dopamine in the striatum.
04:17One effect of this seems to be the facilitation of activity in the direct pathway.
04:24The indirect pathway model involves GABA neurons that project from the external segment of the
04:29globus pallidus to a region called the subthalamic nucleus.
04:33These globus pallidus neurons typically exert an inhibitory effect on glutamate neurons in
04:38the subthalamic nucleus.
04:40But when the indirect pathway is activated by signals from the cerebral cortex, this causes
04:45the activation of GABA neurons in the striatum, which project to the globus pallidus external
04:49and inhibit the activity of neurons there.
04:52This keeps the globus pallidus external neurons from being able to inhibit neurons in the subthalamic
04:57nucleus, freeing up the subthalamic nucleus neurons to stimulate GABA neurons in the globus
05:02pallidus internal segment and the substantia nigra pars reticulata.
05:07These GABA neurons in turn project to the thalamus, inhibiting thalamic neurons that travel to motor
05:12regions of the cerebral cortex to stimulate movement.
05:15The inhibition of these thalamic neurons thus inhibits movement.
05:19This activity in the indirect pathway is thought to antagonize the activity of the direct pathway,
05:24and act to keep unwanted movements from occurring.
05:28Neurons from the substantia nigra pars compacta travel to the striatum via the nigrostriatal pathway,
05:33and they can modulate the activity of the indirect pathway through dopamine release in the striatum.
05:38One effect of this seems to be the inhibition of activity in the indirect pathway, which
05:43leads to the facilitation of movement.
05:45This is thought to be one reason why dopamine depletion in disorders like Parkinson's disease
05:50may lead to difficulties initiating movement.
05:55Just as the basal ganglia may help select and refine movements, they have also been hypothesized
06:01to help select and regulate a wide range of non-motor functions, including cognitive, emotional,
06:06and motivational processes.
06:09In this sense, the basal ganglia can be viewed as a general-purpose system for shaping certain
06:14aspects of both movement-related and non-movement-related behavior.
06:19This perspective has also led to hypothesized roles for the basal ganglia in a number of non-motor
06:25disorders, such as addiction and obsessive-compulsive disorder.
06:30Much like motor circuits, non-motor basal ganglia circuitry typically runs in loops from the cortex
06:37to the basal ganglia, then to the thalamus and back to the cortex.
06:42One prominent non-motor loop, for example, involves the prefrontal cortex, and is thought
06:47to potentially be important for higher-order cognitive functions such as attention, decision-making,
06:52and working memory.
06:55Another loop involves limbic regions like the amygdala, and is thought to be involved with
06:58emotion and motivation.
07:02The basal ganglia are believed to play an important role in learning, particularly forms
07:06of learning that depend on feedback and reinforcement.
07:10Dopamine signaling in the basal ganglia about expected rewards and actual results is thought
07:15to be able to influence basal ganglia circuitry, causing behaviors, thoughts, or strategies
07:20that led to favorable outcomes to be reinforced.
07:24Similar mechanisms are thought to be important for habit formation, where actions or cognitive
07:28routines become more automatic with repetition, another process that the basal ganglia are considered
07:33important in.
07:40Parkinson's disease is considered a neurodegenerative disease because it involves a degeneration and
07:45death of neurons.
07:46It is most frequently seen in adults over the age of 50.
07:50The most recognizable symptoms of Parkinson's initially are movement-related, and generally
07:55involve a tremor that is worse when a person is at rest, bradykinesia, which is slowness
08:01of movement, rigidity, and postural impairment.
08:08Parkinson's patients also often experience non-motor symptoms like cognitive impairment or
08:12psychiatric symptoms.
08:13The causes of Parkinson's are not fully understood, but a combination of genetic and environmental
08:18factors is likely involved.
08:22Parkinson's patients have low levels of the neurotransmitter dopamine in the basal ganglia,
08:26a group of structures involved with movement, among other functions.
08:30These low dopamine levels in the basal ganglia are caused by the death of dopamine neurons
08:34in a region of the basal ganglia called the substantia nigra.
08:37The substantia nigra has high numbers of dopamine neurons, but by the end stages of Parkinson's,
08:43patients have often lost more than half of the dopamine neurons in this region.
08:49The most common treatment for Parkinson's involves an attempt to restore depleted dopamine levels
08:53in the basal ganglia.
08:55Because dopamine does not cross the blood-brain barrier, dopamine cannot simply be administered
08:59to a patient.
09:01Instead, however, patients can be given a precursor to dopamine called L-DOPA.
09:05L-DOPA can cross the blood-brain barrier and is used by the brain to synthesize more dopamine.
09:10This can lead to improvement in the motor symptoms of Parkinson's, but L-DOPA does not halt the neurodegeneration
09:15that occurs in Parkinson's disease.
09:17And, long-term use of L-DOPA can cause a number of side effects, including movement-related
09:22problems.
09:23So it's not a cure for the disease and other treatments are still being explored.
09:29The symptoms of Huntington's disease typically emerge during middle age, and at first often
09:34involve subtle changes in personality, cognition, and movement.
09:38Eventually the symptoms progress into substantial movement problems, like chorea, which involves
09:43uncontrolled spasmodic movements, impaired coordination and balance, muscle rigidity, and difficulty
09:50speaking and or swallowing.
09:52Cognitive and psychiatric symptoms like dementia and depression occur as well.
09:56The disease is incurable and fatal.
10:01These symptoms are associated with neurodegeneration, or the deterioration and death of neurons.
10:06A group of structures called the basal ganglia are strongly affected, but other regions of
10:11the brain experience neurodegeneration as well.
10:16The pathology of Huntington's disease can be traced back to a mutation in a single gene
10:20called Huntington.
10:21The mutation that causes Huntington's disease is a dominant mutation.
10:25Thus, if one parent has the disease, their child has a 50% chance of developing it too.
10:30The Huntington gene contains a DNA sequence that consists of three nucleotides, cytosine, adenine,
10:36and guanine in repetition, a pattern known as a trinucleotide repeat.
10:41When the gene is mutated, an excess number of repeats can occur, and a mutated form of
10:45Huntington protein is created.
10:47The higher the number of repeats, the greater the risk of disease, and all people with 40
10:52or more repeats in the Huntington gene will develop Huntington's disease.
10:56Mutated Huntington proteins have a tendency to group together, forming clusters within
11:00neurons that are not easily removed by brain enzymes.
11:03It has been hypothesized these clusters may play a role in the neurodegeneration seen in
11:08Huntington's disease, for their accumulation in the brain is associated with increased neurodegeneration.
11:16Obsessive-compulsive disorder, or OCD, is a condition characterized by obsessions and or
11:21compulsions.
11:22Obsessions are recurrent unwanted thoughts, while compulsions are repetitive behaviors or
11:27mental acts often performed in response to obsessions, typically with the goal of reducing
11:31anxiety and discomfort.
11:33It's important to note that OCD is often very distressing, and is not just a preference
11:37for orderliness, as the term is sometimes used to imply.
11:41The neuroscience of OCD is not completely understood, and it's likely that different neural circuits
11:47may be involved based on a person's age and symptom profile, among other factors.
11:51One supported perspective on the neuroscience of OCD, however, points to a prominent role
11:56for circuits that connect the orbitofrontal cortex with a group of structures called the
12:00basal ganglia.
12:01According to this perspective, increased activity in the orbitofrontal cortex is associated with
12:06a heightened focus on concerns that spawn obsessive thoughts.
12:09When the orbitofrontal cortex is activated in response to something the brain perceives as
12:13a danger or concern, it communicates with the basal ganglia.
12:17A simplified version of basal ganglia circuitry suggests it consists of two opposing pathways,
12:23an excitatory pathway called the direct pathway, and an inhibitory pathway called the indirect
12:28pathway.
12:29When the orbitofrontal cortex sends a signal to the basal ganglia, it often leads to an
12:33action designed to alleviate the discomfort caused by the perceived danger.
12:37That action is mediated by the direct pathway.
12:40In a healthy person, the indirect pathway then inhibits further action.
12:44In someone with OCD, however, the direct pathway is overexcitable, drowning out the activity
12:50of the indirect pathway and causing a difficult time switching to a different behavior or turning
12:54focus away from the concern causing the discomfort.
12:57Thus, according to this model, overactivity in the orbitofrontal cortex and the direct pathway
13:02of the basal ganglia increases the occurrence of both obsessions and compulsions.
13:12Tourette's syndrome is characterized by recurrent involuntary movements or sounds called tics.
13:17Tics can be classified as simple or complex.
13:21Simple tics usually involve only one group of muscles, and might consist of actions like
13:25eye blinking or throat clearing.
13:28Complex tics are more elaborate, and might involve actions like reaching out to touch something,
13:32or the involuntary use of obscene language, which is known as coprolalia.
13:36It's worth noting that coprolalia, while often associated with Tourette's syndrome, is actually
13:41thought to occur in less than 20% of cases.
13:45The neuroscience of Tourette's syndrome is still poorly understood, but a number of studies
13:49suggest an important role for a group of structures known as the basal ganglia, which includes
13:54the caudate, putamen, globus pallidus, substantia nigra, and subthalamic nucleus.
14:00The basal ganglia are involved in diverse brain functions, but they are especially relevant
14:05to Tourette's syndrome for their hypothesized role in suppressing unwanted actions.
14:10According to this perspective, one function of basal ganglia circuitry is to inhibit neurons
14:15in the thalamus and prevent them from sending undesired movement-related signals to the motor
14:20cortex.
14:21In Tourette's syndrome, it's thought that faulty inhibitory mechanisms in the basal ganglia
14:26ganglia may fail to stop unwanted signals from reaching the cortex.
14:30This causes the execution of an action that the patient might prefer to suppress, forming
14:34the basis for ticks.
14:36The failed inhibition in the basal ganglia is thought to be coupled with increased activity
14:40and motor pathways that generate movements.
14:43Thus, patients with Tourette's might experience a problematic combination of high motor activity
14:48that generates habitual patterns of behavior, along with abnormally low inhibitory activity that
14:53would normally keep those behaviors from being acted out.
14:56More research needs to be done, however, to fully elucidate the neural circuitry underlying
15:01the disorder.
