The basal ganglia (BG) or basal nuclei are a group of subcortical nuclei (cluster of neurons) found in the brains of vertebrates. Positioned at the base of the forebrain and the top of the midbrain, they have strong connections with the cerebral cortex, thalamus, brainstem and other brain areas. The basal ganglia are associated with a variety of functions, including regulating voluntary motor movements, procedural learning, habit formation, conditional learning, eye movements, cognition, and emotion.
The main functional components of the basal ganglia include the striatum, consisting of both the dorsal striatum (caudate nucleus and putamen) and the ventral striatum (nucleus accumbens and olfactory tubercle), the globus pallidus, the ventral pallidum, the substantia nigra, and the subthalamic nucleus. Each of these components has complex internal anatomical and neurochemical structures. The largest component, the striatum (dorsal and ventral), receives input from various brain areas but only sends output to other components of the basal ganglia. The globus pallidus receives input from the striatum and sends inhibitory output to a number of motor-related areas. The substantia nigra is the source of the striatal input of the neurotransmitter dopamine, which plays an important role in basal ganglia function. The subthalamic nucleus mainly receives input from the striatum and cerebral cortex and projects to the globus pallidus.
The basal ganglia are thought to play a key role in action selection, aiding in the choice of behaviors to execute. More specifically, they regulate motor and premotor cortical areas, facilitating smooth voluntary movements. Experimental studies show that the basal ganglia exert an inhibitory influence on a number of motor systems, and that a release of this inhibition permits a motor system to become active. The "behavior switching" that takes place within the basal ganglia is influenced by signals from many parts of the brain, including the prefrontal cortex, which plays a key role in executive functions. It has also been hypothesized that the basal ganglia are not only responsible for motor action selection, but also for the selection of more cognitive actions. Computational models of action selection in the basal ganglia incorporate this.
The basal ganglia are of major importance for normal brain function and behaviour. Their dysfunction results in a wide range of neurological conditions including disorders of behaviour control and movement, as well as cognitive deficits that are similar to those that result from damage to the prefrontal cortex. Those of behaviour include Tourette syndrome, obsessive–compulsive disorder, and addiction. Movement disorders include, most notably Parkinson's disease, which involves degeneration of the dopamine-producing cells in the substantia nigra; Huntington's disease, which primarily involves damage to the striatum;
Structure
In terms of the development of the nervous system in humans, the central nervous system is often classified based on the original three primitive brain vesicles: These primary vesicles form in the normal development of the neural tube of the embryo and initially include the prosencephalon, mesencephalon, and rhombencephalon, in rostral to caudal (from head to tail) orientation. Later in development each section itself turns into smaller components. During development, the cells that migrate tangentially to form the basal ganglia are directed by the lateral and medial ganglionic eminences. The following table demonstrates this developmental classification and traces it to the anatomic structures found in the basal ganglia. The structures relevant to the basal ganglia are shown in bold.
{| class="wikitable"
! scope="col" | Primary division of the neural tube
! scope="col" | Secondary subdivision
! scope="col" | Final segments in a human adult
|-
! scope="row" | Prosencephalon
|
- Telencephalon
- Diencephalon
|
- On each side of the brain: the cerebral cortices, caudate, putamen, Globus pallidus, ventral pallidum
- Thalamus, subthalamus, epithalamus, hypothalamus, subthalamic nucleus
|-
! scope="row" | Mesencephalon
|
- Mesencephalon
|
- Mesencephalon (midbrain): substantia nigra pars compacta (SNc), substantia nigra pars reticulata (SNr)
|-
! scope="row" | Rhombencephalon
|
- Metencephalon
- Myelencephalon
|
- Pons and cerebellum
- Medulla
|-
|}
thumb|Video of relevant anatomy
thumb|400px|[[Anatomical terms of location|Coronal slices of human brain showing the basal ganglia. White matter is shown in dark gray, gray matter is shown in light gray.<br />Anterior: striatum, globus pallidus (GPe and GPi)<br />Posterior: subthalamic nucleus (STN), substantia nigra (SN)]]
The basal ganglia form a fundamental component of the cerebrum. In contrast to the cortical layer that lines the surface of the forebrain, the basal ganglia are a collection of distinct masses of gray matter lying deep in the brain not far from the junction of the thalamus. They lie to the side of and surround the thalamus. Like most parts of the brain, the basal ganglia consist of left and right sides that are virtual mirror images of each other.
In terms of anatomy, the basal ganglia are divided into four distinct structures, depending on how superior or rostral they are (in other words depending on how close to the top of the head they are): Two of them, the striatum and the pallidum, are relatively large; the other two, the substantia nigra and the subthalamic nucleus, are smaller. In the illustration to the right, two coronal sections of the human brain show the location of the basal ganglia components. Of note, and not seen in this section, the subthalamic nucleus and substantia nigra lie farther back (posteriorly) in the brain than the striatum and pallidum.
Striatum
thumb|left|220px|Basal ganglia
The striatum is a subcortical structure generally divided into the dorsal striatum and ventral striatum. The dorsal striatum is further divided into a dorsomedial and dorsolateral striatum.
The striatum is composed mostly of medium spiny neurons. These GABAergic neurons project to the external (lateral) globus pallidus and internal (medial) globus pallidus as well as the substantia nigra pars reticulata. The projections into the globus pallidus and substantia nigra are primarily dopaminergic, although enkephalin, dynorphin and substance P are expressed. The striatum also contains interneurons that are classified into nitrergic neurons (due to use of nitric oxide as a neurotransmitter), tonically active (i.e. constantly releasing neurotransmitter unless inhibited) cholinergic interneurons, parvalbumin-expressing neurons and calretinin-expressing neurons. The dorsal striatum receives significant glutamatergic inputs from the cortex, as well as dopaminergic inputs from the substantia nigra pars compacta. The dorsal striatum is generally considered to be involved in sensorimotor activities. The ventral striatum receives glutamatergic inputs from the limbic areas as well as dopaminergic inputs from the VTA, via the mesolimbic pathway. The ventral striatum is believed to play a role in reward and other limbic functions. The dorsal striatum is divided into the caudate and putamen by the internal capsule while the ventral striatum is composed of the nucleus accumbens and olfactory tubercle. The caudate has three primary regions of connectivity, with the head of the caudate demonstrating connectivity to the prefrontal cortex, cingulate cortex and amygdala. The body and tail show differentiation between the dorsolateral rim and ventral caudate, projecting to the sensorimotor and limbic regions of the striatum respectively. Striatopallidal fibres connect the striatum to the pallidus.
Pallidum
The pallidum consists of a large structure called the globus pallidus ("pale globe") together with a smaller ventral extension called the ventral pallidum. The globus pallidus appears as a single neural mass, but can be divided into two functionally distinct parts, the internal globus pallidus (GPi) and the external globus pallidus (GPe). The circuitry model has evolved since the first proposed model in the 1990s by DeLong in the parallel processing model, in which the cortex and substantia nigra pars compacta project into the dorsal striatum giving rise to an inhibitory indirect and excitatory direct pathway.
- The inhibitory indirect pathway involved the inhibition of the globus pallidus externus, allowing for the disinhibition of the globus pallidus internus (through STN) allowing it to inhibit the thalamus.
- The direct or excitatory pathway involved the disinhibition of the thalamus through the inhibition of the GPi/SNr. However the speed of the direct pathway would not be concordant with the indirect pathway in this model leading to problems with it. To get over this, a hyperdirect pathway where the cortex sends glutamatergic projections through the subthalamic nucleus exciting the inhibitory GPe under the center surround model, as well as a shorter indirect pathway have been proposed.
While implemented as a gradient without exact borders (or septa within the nuclei), the basal ganglia circuitry has often been divided into five pathways: one limbic, two associative (prefrontal), one oculomotor, and one motor pathway. The motor and oculomotor pathways are sometimes grouped into one motor pathway. Furthermore, a simplified scheme into three domains (motor, associative and limbic) has gained popularity. The five general pathways are organized as follows:
- The motor loop involving projections from the supplementary motor area, arcuate premotor area, primary motor cortex and somatosensory cortex into the putamen, which projects into the ventrolateral GPi and caudolateral SNr which projects into the cortex through the ventralis lateralis pars medialis and ventralis lateralis pars oralis.
- The oculomotor loop involved projections from the frontal eye fields, the dorsolateral prefrontal cortex (DLPFC), and the posterior parietal cortex into the caudate, into the caudal dorsomedial GPi and ventrolateral SNr, finally looping back into the cortex through the lateral ventralis anterior pars magnocellularis(VAmc).
- The first cognitive/associative pathway proposes a pathway from the DLPFC, into the dorsolateral caudate, followed by a projection into the lateral dorsomedial GPi, and rostral SNr before projecting into the lateral VAmc and medial pars magnocellularis.
- The second cognitive/associative pathway proposed is a circuit projecting from the lateral orbitofrontal cortex, the temporal gyrus, and anterior cingulate cortex into the ventromedial caudate, followed by a projection into the lateromedial GPi, and rostrolateral SNr before looping into the cortex via the medial VAmc and medial magnocellularis.
- The limbic circuit involving the projections from the ACC, hippocampus, entorhinal cortex, and insula into the ventral striatum, then into the rostrodorsal GPi, ventral pallidum and rostrodorsal SNr, followed by a loop back into the cortex through the posteromedial part of the medial dorsal nucleus. However, more subdivisions of loops have been proposed, up to 20,000.
These circuits are known to interact (at least) on a cortico-cortical level (U-fibers), a cortico-striatal level (by diffuse projections from cortex to striatum), a thalamo-cortical level (by diffuse reciprocal connections across thalamus and cortex) and striato-nigral level. The latter interaction has been characterized in more detail by Suzanne Haber and colleagues in their 'spiral model', which postulated how the ventral striatum (limbic circuit) can influence the dorsal striatum (motor circuit) through the midbrain dopamine cells (ventral tegmental area, substantia nigra pars compacta and other regions). In this model, connections from the ventral tegmental area to the shell region of the nucleus accumbens form a "closed," reciprocal loop. However, these projections also extend laterally to influence dopamine neurons that send signals to the rest of the ventral striatum, creating the initial segment of a feed-forward loop, or 'spiral'. This spiral continues through striato-nigro-striatal pathways, whereby the VS affects cognitive and motor striatal areas via midbrain dopamine neurons.
The direct pathway, originating in the dorsal striatum inhibits the GPi and SNr, resulting in a net disinhibition or excitation of the thalamus. This pathway consists of medium spiny neurons (MSNs) that express dopamine receptor D1, muscarinic acetylcholine receptor M4, and adenosine receptor A1. This pathway has been proposed to result in global motor inhibition(inhibition of all motor activity), and termination of responses. Another shorter indirect pathway has been proposed, which involves cortical excitation of the subthalamic nucleus resulting in direct excitation of the GPe, and inhibition of the thalamus. This pathway is proposed to result in inhibition of specific motor programs based on associative learning. This hyperdirect pathway is proposed to inhibit premature responses, or globally inhibit the basal ganglia to allow for more specific top down control by the cortex.
Functional connectivity
The functional connectivity, measured by regional co-activation during functional neuroimaging studies, is broadly consistent with the parallel processing models of basal ganglia function. The putamen was generally coactivated with motor areas such as the supplementary motor area, caudal anterior cingulate cortex and primary motor cortex, while the caudate and rostral putamen were more frequently coactivated with the rostral ACC and DLPFC. The ventral striatum was significantly associated with the amygdala and hippocampus, which although was not included in the first formulations of basal ganglia models, has been an addition to more recent models.
Function
===Eye movements=== <!-- Please preserve this link. It is used elsewhere -->
One intensively studied function of the basal ganglia is its role in controlling eye movements. Eye movement is influenced by an extensive network of brain regions that converges on a midbrain area called the superior colliculus (SC). The SC is a layered structure whose layers form two-dimensional retinotopic maps of visual space. A "bump" of neural activity in the deep layers of the SC drives an eye movement directed toward the corresponding point in space.
The SC receives a strong inhibitory projection from the basal ganglia, originating in the substantia nigra pars reticulata (SNr).
Decision making
Two models have been proposed for the basal ganglia's role in decision making. In the first, actions are generated by a "critic" in the ventral striatum that estimates value, and the actions are carried out by an "actor" in the dorsal striatum. In the second, the basal ganglia acts as a selection mechanism, where actions are generated in the cortex and are selected based on context by the basal ganglia. The CBGTC loop is also involved in reward discounting, with firing increasing with an unexpected or greater than expected reward. One review supported the idea that the cortex was involved in learning actions regardless of their outcome, while the basal ganglia was involved in selecting appropriate actions based on associative reward based trial and error learning.
Working memory
The basal ganglia has been proposed to gate what does and does not enter working memory. One hypothesis proposes that the direct pathway (Go, or excitatory) allows information into the prefrontal cortex, where it stays independent of the pathway, while another theory proposes that in order for information to stay in the prefrontal cortex, the direct pathway needs to continue reverberating. The short indirect pathway has been proposed to close the gate to the prefrontal cortex, in a direct push-pull antagonism with the direct pathway. Together these mechanisms regulate working memory focus.
The following is a list of disorders, conditions, and symptoms that have been linked to the basal ganglia: