Deep inside the brain lies a collection of nuclei collectively known as the basal ganglia. Most notable, the basal ganglia control a wide range of movements from the eyes to the muscles of the extremities. Basal ganglia disease can cause psychological and physical impairment.
The basal ganglia is a collection of nuclei responsible for feedback from several different sources within the brain. The basal ganglia relay information to the cortex via the thalamus. It is responsible for the control of descending motor pathways and controls excessive or exaggerated movements.
There are several life-altering conditions and diseases associated with the basal ganglia. Many of them are sudden-onset in newborn children or toddlers like PANDAS, while some are only noticeable in older patients such as Parkinson’s.
The Structure Of The Basal Ganglia
The basal ganglia is not a singular structure but a combination of structures deep in the basal area of the brain. It is made up of the following.
The striatum is made up of spiny neurons, and the subcortical structure of the striatum is divided into the:
- Dorsal striatum and
- Ventral Striatum
The striatum contains interneurons classified into:
- Tonically active
- Parvalbumin- expressing neurons
- Nitrergic neurons
- Cholinergic neurons
- Claretenin-expressing neurons
The dorsal striatum is involved in sensorimotor activities such as:
- vestibular and
It receives glutamatergic input from the cortex and dopaminergic inputs from the substantia nigra pars compacta. It is divided into the putamen and caudate by the internal capsule.
The caudate has three regions of connectivity, namely:
- The caudate head is connected to the prefrontal cortex, amygdala, and cingulate cortex
- The tail and body differentiate between the ventral caudate and the dorsolateral rim and project to the striatum's limbic and sensorimotor regions.
- The striatum is connected to the pallidus via striatopallidal fibers.
The pallidum is a large structure known as the globus pallidus. With it is a ventral extension known as the ventral pallidum. Although it looks like a single object or mass, it can be divided into two distinct parts.
- The medial or internal segment– GPi is the abbreviation
- The lateral or external segment – GPe is the abbreviation
The medial and lateral segments both contain GABAergic neurons. The result is inhibitory on the target. Each segment participates in distinct neural circuits. The GPi segment receives direct and indirect signals from the striatum. The GPe receives largely from the striatum and relays to the subthalamic nucleus.
Pallidal neurons fire at a high but steady rate even in input absence. Signals to the pallidal neurons from the striatum can cause an increase or reduction in the firing rate.
The Substantia Nigra
The midbrain gray matter section of the basal ganglia is called the substantia nigra. It has two parts, namely:
- The pars reticulata or SNr and
- The pars compacta or SNc
The SNr/GPi complex works in unison and inhibits the thalamus. The SNc produces dopamine, a powerful neurotransmitter. Dopamine helps to maintain balance in the striatal pathway.
The Subthalamic Nucleus
The only section of the basal ganglia producing the excitatory neurotransmitter glutamate is the subthalamic nucleus and is the diencephalic gray matter section of the ganglia. Its part of the indirect pathway, and its role is stimulation of the SNr-GPi complex. It receives inhibitory input from the globus pallidus and forwards excitatory input to the medial segment.
The Circuit Connections
There is still much debate regarding the ganglia function and circuits and the pathways and divisions, whether they overlap and how they are regulated.
The circuitry of the basal ganglia is divided into five distinct pathways:
- Two prefrontal or associative pathways
- One limbic pathway
- One motor pathway
- One ocular pathway
Some of the five pathways are explained as follows.
The Limbic Pathway
The limbic circuit projections follow the ACC with the hippocampus, insula, and entorhinal cortex into the ventral striatum. From there into the rostrodorsal GPi, the ventral pallidum and rostrodorsal SNr. From there, back into the cortex via the posteromedial section of the medial dorsal nucleus.
The Two Prefrontal/Associative Pathways
The oculomotor loop involves projections from the arcuate premotor and supplementary motor area, from the somatosensory and motor cortex into the putamen. Projecting into the caudolateral SNr and ventrolateral GPI and collectively projected into the cortex from the ventralis lateralis pars oralis and ventralis lateralis pars medialis.
The second oculomotor loop involves projections from the dorsolateral prefrontal cortex, the frontal eye fields, and posterior parietal cortex into the caudate and caudal dorsomedial GPi and ventrolateral SNr. It circles back to the cortex through the lateral ventralis anterior pars magnocellularis.
There are several afferent glutamatergic inputs contained in the basal ganglia. There are many neuropeptides found in the basal ganglia, including:
- Substance P
- Neurokinin A
- Neurokinin B
- Neuropeptide Y
There are more neuromodulators found in the basal ganglia, such as:
- Carbon monoxide
- Nitric oxide
Function Of The Basal Ganglia
Apart from the chemical interactions, the basal ganglia have a wide-ranging function in the body. Some of the most notable functions are.
One of the basal ganglia's significant roles is controlling eye movements. All eye movement is affected by a vast network in the brain. They congregate in the superior colliculus in the midbrain region.
The superior colliculus's layered structure can form 2-dimensional retinotopic visual space maps. When there is a change in a visual point in space, that surge of neural activity in the layers of the superior colliculus directs eye movement to that point.
The basal ganglia send strong inhibitory projection to the superior colliculus, which originates in the SNr or substantia nigra pars reticulata. While the SNr neurons fire at a very high, continuous rate, it pauses at the onset of eye movement. This releases the substantia nigra pars reticulata from inhibition.
Any eye movement is associated with the SNr pause, but only some neurons are more dominant where eye movement is concerned. For example, the caudate nucleus contains some neurons that show activity when there is any eye movement.
Caudate nucleus cells typically fire at a low rate, so the increase in activity is very noticeable when there is eye movement. Activation in the caudate nucleus means there is eye movement. This will inhibit the substantia nigra pars reticulata through direct GABAergic projections. The superior colliculus becomes disinhibited in this process.
Role In Motivation
The role of extracellular dopamine in the body is linked to various motivation levels. The three notable levels are:
- High levels of extracellular dopamine – linked to a satiated state
- Medium levels of extracellular dopamine – linked to a seeking state
- Low levels of extracellular dopamine – linked to aversion
Extracellular dopamine greatly influences the limbic basal ganglia. The ventral pallidum, substantia nigra pars reticulata, and the entopeduncular nucleus are inhibited by increased dopamine, but the thalamus is disinhibited as a result.
The ventral striatum and prefrontal cortex become activated when the thalamus is disinhibited. This increase in D1 leads to reward. The evidence in primate studies shows that the subthalamic nucleus and the globus pallidus are also involved in processing rewards.
There are two parts involved in the decision-making aspect of the basal ganglia. The one generates actions, and the other carries them out.
- The ventral striatum is the critic – generates the actions
- The dorsal striatum is the actor – carries out the actions
It is assumed that actions are generated in the cortex, and depending on the context, the basal ganglia will select which action to act on. The cortex can learn an action regardless of the outcome. However, the basal ganglia select actions based on the outcome or greater reward or error.
The basal ganglia can be akin to a gatekeeper where memory is concerned. It decides what may or may not enter working memory. It is believed that the excitatory pathway allows information into the prefrontal cortex.
For the information to stay in the prefrontal cortex, it must continue reverberating. The direct and indirect pathways are mechanisms regulating working memory focus.
Clinical Significance – The Basal Ganglia And Disease
There is a group of movement diseases that stem from the basal ganglia. They result in two distinct outcomes.
- Hyperkinetic disorders – Insufficient output
- Hypokinetic disorders – Excessive output
Hyperkinetic disorders result from a low output from the basal ganglia to the thalamus. This results in the thalamus not having sufficient inhibition of the cortex and thalamic projections. This creates involuntary or uncontrolled movements.
Hypokinetic disorders result from an excess of output from the basal ganglia. This inhibits output from the thalamus to the cortex, and voluntary movement becomes limited.
In earlier times, anatomists who didn’t know much about neurochemistry or cellular architecture believed the basal ganglia to be a separately functioning unit by grouping them based on anatomical structure.
As is known, the basal ganglia are made up of a single structure, although there are distinctive components such as the putamen and caudate nucleus that have special functions, such as the globus pallidus, which function independently.
The basal ganglia are located in the forebrain's basal part, the origin of the term basal. The ganglia part of the name is a contradiction in this case. Modern medicine uses the term ganglia to refer to nuclei – the neural clusters of the peripheral nervous system.
The basal ganglia are also commonly referred to as the basal nuclei or the international standard for naming the anatomy – nuclei basales.
Common Disorders Linked To The Basal Ganglia
Because the basal ganglia are responsible for a network of functions that control movement, several disorders and diseases are linked to affected basal ganglia. The list of diseases or disorders commonly associated are:
- Addiction – The basal ganglia control the reward or pleasure center, and addiction is an ongoing input and reward cycle, albeit destructive.
- Athetosis – Slow, involuntary movements of the limbs, fingers, and face.
- Athymhormic syndrome – Excessive apathy or lack of motivation
- Attention-deficit hyperactivity disorder or ADHD
- Blepharospasm – Abnormal eyelid contraction
- Bruxism – Excessive or obsessive teeth grinding
- Cerebral palsy - Damage to the basal ganglia during the second or third trimester of pregnancy
- Chorea – Involuntary and abnormal body movements
- Dystonia – Slow, repetitive movement and involuntary muscle movements
- Epilepsy – A brain disorder characterized by repeated seizures.
- Fahr's disease – Abnormal calcium deposits in the brain.
- Foreign accent syndrome – A sudden accent change after a head injury
- Huntington's disease – Progressive nerve cell breakdown of the brain.
- Kernicterus – Unresponsive jaundice in newborn babies
- Lesch–Nyhan syndrome – Abnormal behavior due to excessive buildup of uric acid
- Major depressive disorder – Persistently depressive mood and loss of interest in general activities
- Obsessive-compulsive disorder – A mental disorder that causes repetitive thoughts or actions
- PANDAS (disorder) – An autoimmune neuropsychiatric disorder caused by a Streptococcus infection
- Parkinson's disease – A brain disease that causes involuntary movements and body stiffness
- Restless legs syndrome – Unpleasant and involuntary leg movements when the person is at rest
- Spasmodic dysphonia – Involuntary spasms of the larynx
- Stuttering – Involuntary voice movements
- Sydenham's chorea – A childhood neurological disease that causes involuntary movements of the hands, body, and trunk
- Tardive dyskinesia - A side effect of certain medicines that cause rapid blinking, lip movements, and tongue trusting.
- Tourette's disorder – A disorder that causes involuntary words, expletives, tics, and sounds.
- Wilson's disease – A disease that stores excess copper in the brain, liver, and corneas.
The Basal Ganglia In Vertebrates
All vertebrates have basal ganglia that form a part of the forebrain. Even though it is considered to be the most primitive of vertebrates, the lamprey fish also has anatomically visible elements of pallidal, striatal, and nigral basal ganglia.
Different species of vertebrates have different names for the basal ganglia. The different names in some species are as follows:
- Internal globus pallidus becomes the entopeduncular nucleus– in rodents and cats.
- Striatum becomes the paleostriatum augmentatum – birds
- External globus pallidus becomes the paleostriatum primitivum – birds
One controversy in the comparative anatomy regarding the basal ganglia as a convergent is its development through phylogenesis. The debate is surrounding the degree to which selective processing takes place. This is compared to the corresponding processing contained in the basal ganglia re-entry loops.
How Are Diseases Of The Basal Ganglia Diagnosed?
Diseases that affect the basal ganglia in newborn children or toddlers often characteristically present as movement disturbances or twitches. Clinical and experimental evidence suggests that the basal ganglia are crucial in the mental state of an individual.
The basal ganglia may be affected by degenerative or neurometabolic diseases but should be distinguished. Ischemic or chemical trauma causes clinical changes to the basal ganglia due to its susceptibility to metabolic abnormalities.
Because other diseases may present similarly in neuroradiological investigations, diagnoses of basal ganglia diseases suggest repeated MRI scans. The frequency of MRI scans will greatly depend on the myelination or development stage of the patient’s brain.
Several radiological and clinical findings will be consulted to establish a firm diagnosis of basal ganglia disease. For early diagnoses of neurometabolic basal ganglia disease, a neuroimaging of the brain in combination with therapies can be used to monitor any minor or major changes.
The following testing methods may be applied to confirm a basal ganglia disease diagnosis –
- MRI or CT scan of the head/brain
- MRA or Magnetic Resonance Angiography to view the arteries and veins in the brain
- Genetic tests
- Full blood screening – Thyroid function, liver function, iron levels, copper levels, blood sugar levels.
- PET or Positron Emission Tomography scan to establish the brain metabolism.
What Treatments Are Available For Diseases Affecting The Basal Ganglia?
The brain has a remarkable self-healing method called neuroplasticity, which means the ability to re-wire and heal in time. In basal ganglia disease, neuroplasticity is one of the best treatment methods.
Physiotherapy and repetitive muscle exercise to re-wire neural pathways and strengthen the affected muscles or limbs are used to rehabilitate the body while coping with basal ganglia disease.
Alongside the physical therapy with a physiotherapist and occupational therapist, neurorehabilitation devices should be used between sessions. Here are more options for the effective treatment of basal ganglia disease.
- Surgical Intervention – As a drastic measure, a thalamotomy may be suggested in severe cases of basal ganglia disease. This procedure removes the area of the brain that controls involuntary muscle movement.
- Botulinum Injections Or Botox – Botox injections block nerve signals in targeted areas. The muscle spasms and movements are drastically reduced, and the effect lasts for several weeks and sometimes months.
- Prescribed Medication - Depending on the suggested and recommended course of treatment, doctors mayprescribe medications such as baclofen intrathecally for sclerosis, penicillin in the case of PANDAS, and carbidopa-levodopa for Parkinson's.
The basal ganglia are important for fine-tuning and controlling voluntary muscle movements. Any disturbance or disease affecting areas within the basal ganglia will present a deviation or lack of control in regular functions.
Many physical impairments resulting from basal ganglia disease or damage often result in a psychological decline and require treatment.