Globus Pallidus (Internal)

The internal globus pallidus, also called the globus pallidus internus (GPi) or internal pallidal segment, is the medial division of the globus pallidus and one of the principal output nuclei of the basal ganglia. It lies deep within each cerebral hemisphere and forms the medial part of the globus pallidus, immediately medial to the external globus pallidus.

The GPi contains predominantly GABAergic projection neurons that are tonically active. These neurons receive information processed through the direct, indirect, and hyperdirect basal ganglia pathways and send inhibitory output primarily to nuclei of the thalamus and selected brainstem structures.

Through these connections, the internal globus pallidus regulates the activity of motor, premotor, associative, and related cortical networks. Its position at the output stage of basal ganglia circuitry also makes it clinically important in movement disorders and a major target for deep brain stimulation.

Location

The internal globus pallidus lies deep within the cerebral hemisphere as the medial segment of the globus pallidus.

It is positioned medial to the external globus pallidus and lateral to the internal capsule. Together with the external segment, it forms the globus pallidus.

The putamen lies lateral to both pallidal segments, and the putamen together with the globus pallidus forms the lentiform nucleus.

General Features

Feature	Description
Full name	Internal globus pallidus
Alternative term	Globus pallidus internus (GPi)
Location	Deep cerebral hemisphere
Position	Medial segment of globus pallidus
Major neurotransmitter	GABA
Neuronal activity	Predominantly tonic inhibitory activity
Major targets	Thalamic and brainstem nuclei
Major role	Principal output structure of the basal ganglia

Globus Pallidus

The globus pallidus is a mass of gray matter located medial to the putamen. It appears relatively pale in gross sections because of the numerous myelinated fibers passing through the structure.

It is divided into external and internal segments by a thin sheet of myelinated fibers known as the medial medullary lamina.

The two pallidal segments are anatomically adjacent but have different connections and functional roles.

Internal and External Segments

The internal globus pallidus is the medial pallidal segment, while the external globus pallidus (GPe) lies immediately lateral to it.

The GPe functions primarily as an intrinsic regulatory component of basal ganglia networks and is especially prominent in the indirect pathway.

The GPi, by contrast, provides major inhibitory output from the basal ganglia to the thalamus and other targets.

Internal versus External Globus Pallidus

Feature	Internal Globus Pallidus	External Globus Pallidus
Abbreviation	GPi	GPe
Position	Medial pallidal segment	Lateral pallidal segment
Principal neurotransmitter	GABA	GABA
Major role	Basal ganglia output	Intrinsic basal ganglia regulation
Important targets	Thalamus and brainstem	Subthalamic nucleus and other basal ganglia structures
Clinical DBS target	Yes	Not a standard primary target

Relationship to the Putamen

The putamen lies lateral to the globus pallidus.

A thin layer of white matter, the lateral medullary lamina, separates the putamen from the external pallidal segment. The GPi is therefore separated from the putamen by the GPe and intervening medullary laminae.

The putamen provides important striatal input to pallidal neurons as part of basal ganglia motor circuitry.

Relationship to the External Globus Pallidus

The external globus pallidus lies immediately lateral to the GPi.

The medial medullary lamina separates the two segments anatomically.

Functionally, the GPe influences GPi activity both through direct inhibitory connections and indirectly through its reciprocal interactions with the subthalamic nucleus.

Relationship to the Lentiform Nucleus

The lentiform nucleus consists of the putamen and globus pallidus.

From lateral to medial, its principal components are the putamen, external globus pallidus, and internal globus pallidus.

The GPi therefore forms the most medial major component of the lentiform nucleus.

Relationship to the Internal Capsule

The internal capsule lies medial to the lentiform nucleus and closely borders the internal globus pallidus.

The posterior limb of the internal capsule contains important corticospinal, corticobulbar, and sensory projection fibers near the pallidum.

This close relationship is particularly important during stereotactic procedures because inaccurate placement within the GPi region can affect adjacent internal capsular fibers.

Relationship to the Subthalamic Nucleus

The subthalamic nucleus is functionally closely connected with the internal globus pallidus.

It sends strong glutamatergic excitatory projections to the GPi.

These projections are important components of both indirect and hyperdirect basal ganglia pathways and can increase inhibitory output from the GPi.

Relationship to the Substantia Nigra

The internal globus pallidus is functionally related to the substantia nigra pars reticulata (SNr).

The GPi and SNr are often considered functionally analogous output structures of the basal ganglia because both contain tonically active GABAergic neurons and send inhibitory projections to downstream targets.

Their output territories differ, but together they provide major channels through which basal ganglia processing influences the thalamus and brainstem.

Microscopic Organization

The internal globus pallidus contains projection neurons surrounded by numerous myelinated axons and dendritic processes.

Most principal neurons are GABAergic and possess extensive dendritic fields that receive converging input from striatal, subthalamic, and pallidal sources.

The abundance of myelinated fibers contributes to the relatively pale appearance of the pallidum.

GABAergic Projection Neurons

GABA is the principal neurotransmitter released by projection neurons of the GPi.

These neurons exert inhibitory effects on their thalamic and brainstem targets.

Because many GPi neurons fire continuously at relatively high rates, their targets are maintained under substantial tonic inhibitory influence.

Tonic Inhibitory Activity

Neurons within the GPi typically exhibit spontaneous tonic activity.

This continuous firing produces ongoing inhibition of target structures, particularly motor-related thalamic nuclei.

Basal ganglia pathways regulate behavior partly by changing this tonic pallidal output, thereby increasing or decreasing inhibition of selected downstream targets.

Afferent Connections

The GPi receives important input from the striatum, external globus pallidus, and subthalamic nucleus.

Striatal and external pallidal projections are predominantly GABAergic and inhibitory, whereas subthalamic projections are glutamatergic and excitatory.

The integration of these opposing influences determines the firing pattern of GPi output neurons.

Striatal Input

The striatum sends direct inhibitory projections to the GPi.

These fibers arise from populations of medium spiny neurons associated with the direct basal ganglia pathway.

Activation of these striatal neurons inhibits GPi neurons and can reduce their inhibitory influence on downstream thalamic targets.

Subthalamic Input

The subthalamic nucleus provides one of the major excitatory inputs to the GPi.

Its neurons release glutamate and increase the activity of pallidal output neurons.

Subthalamic excitation of the GPi is an important mechanism within both the indirect and hyperdirect pathways.

External Pallidal Input

The GPe can influence the GPi through inhibitory GABAergic projections.

It also affects GPi activity indirectly by regulating the subthalamic nucleus.

This combination of direct and indirect connections allows the external pallidum to modify basal ganglia output through several routes.

Efferent Connections

The internal globus pallidus sends its principal efferent projections toward the thalamus, with additional projections reaching brainstem structures.

These efferent fibers are predominantly GABAergic and inhibitory.

Pallidothalamic fibers leave the GPi through several characteristic fiber systems before converging toward thalamic targets.

Pallidothalamic Fibers

Pallidothalamic fibers are axons arising primarily from neurons of the internal globus pallidus and projecting toward the thalamus.

Two major bundles are traditionally recognized: the ansa lenticularis and lenticular fasciculus.

These pathways ultimately converge within the subthalamic region before continuing toward thalamic nuclei.

Ansa Lenticularis

The ansa lenticularis is a bundle of pallidofugal fibers arising from the internal globus pallidus.

It curves around the ventral aspect of the internal capsule and passes medially toward the subthalamic region.

Its fibers ultimately join other pallidothalamic pathways traveling toward the thalamus.

Lenticular Fasciculus

The lenticular fasciculus contains pallidal fibers that pass through the internal capsule before coursing medially through the subthalamic region.

It represents another major route by which GPi output reaches the thalamus.

The lenticular fasciculus is sometimes described as the field H2 of Forel within the subthalamic region.

Thalamic Fasciculus

Fibers of the ansa lenticularis and lenticular fasciculus converge within the region of the field H of Forel.

From this region, pallidothalamic fibers continue superiorly as part of the thalamic fasciculus, also associated with field H1 of Forel.

These fibers terminate principally within motor-related thalamic nuclei.

Thalamic Targets

The GPi projects prominently to the ventral anterior and ventral lateral nuclei of the thalamus.

These thalamic nuclei project to motor, premotor, supplementary motor, and related cortical areas.

Through this pathway, changes in GPi activity influence cortical systems responsible for planning and executing movement.

Basal Ganglia Output

The GPi represents one of the final processing stages through which information within basal ganglia circuits reaches structures outside the basal ganglia.

Its output is predominantly inhibitory.

Changes in the firing rate and pattern of GPi neurons therefore determine how strongly selected thalamic and brainstem targets are inhibited.

Direct Pathway

The direct pathway provides a relatively direct route from the striatum to basal ganglia output nuclei.

A simplified sequence is:

Cerebral cortex → striatum → GPi/SNr → thalamus → cerebral cortex.

Cortical input excites the striatum, and activated direct-pathway striatal neurons inhibit GPi output neurons.

Functional Logic of the Direct Pathway

Because the GPi normally exerts tonic inhibition on the thalamus, inhibition of the GPi reduces this inhibitory output.

The resulting disinhibition of selected thalamic neurons allows greater thalamic influence on corresponding cortical networks.

This mechanism contributes to the selection and facilitation of appropriate actions.

Indirect Pathway

The GPi is also the major output destination of activity transmitted through the classical indirect pathway.

A simplified sequence is:

Cerebral cortex → striatum → GPe → subthalamic nucleus → GPi/SNr → thalamus → cerebral cortex.

Through this route, changes in GPe and subthalamic activity ultimately modify GPi output.

Functional Logic of the Indirect Pathway

Activation of indirect-pathway striatal neurons inhibits the GPe, reducing its inhibitory influence on the subthalamic nucleus.

The resulting increase in subthalamic activity excites GPi neurons.

Increased GPi activity strengthens inhibition of selected thalamic targets and contributes to suppression of competing actions.

Hyperdirect Pathway

The hyperdirect pathway connects the cerebral cortex with the subthalamic nucleus without first passing through the striatum.

A simplified sequence is:

Cerebral cortex → subthalamic nucleus → GPi/SNr → thalamus.

This pathway allows cortical activity to rapidly increase basal ganglia output through excitation of the subthalamic nucleus.

Direct, Indirect and Hyperdirect Pathways

Pathway	Major Influence on GPi	General Effect on Selected Thalamic Targets
Direct	Inhibits GPi	Reduces pallidal inhibition
Indirect	Increases GPi activity through STN	Increases pallidal inhibition
Hyperdirect	Rapidly excites GPi through STN	Rapidly increases pallidal inhibition

Dopaminergic Modulation

Dopamine released from neurons of the substantia nigra pars compacta modifies striatal activity and therefore indirectly regulates GPi output.

D1-type receptor signaling generally promotes activity of direct-pathway striatal neurons, while D2-type receptor signaling generally reduces activity of indirect-pathway neurons.

The combined effect supports appropriate modulation of basal ganglia output according to behavioral context.

Disinhibition

Disinhibition is a fundamental organizational principle of basal ganglia circuitry.

Because GPi neurons tonically inhibit their targets, inhibiting the GPi can release selected thalamic neurons from this ongoing inhibition.

Basal ganglia circuits can therefore regulate downstream activity by controlling the degree of tonic pallidal inhibition rather than simply providing direct excitation.

Motor Functions

The GPi contributes to movement by regulating the output of basal ganglia circuits directed toward motor-related thalamic and brainstem structures.

It influences the selection, initiation, scaling, and suppression of movements rather than directly generating motor commands.

Its activity reflects information processed through cortical, striatal, pallidal, and subthalamic networks.

Action Selection

Basal ganglia circuits help select actions appropriate to the current behavioral context while suppressing competing actions.

The GPi occupies a strategic position at the output stage of this process.

Changes in GPi firing can selectively alter the inhibition applied to thalamocortical channels associated with different potential actions.

Movement Facilitation

Reduced inhibitory output from selected populations of GPi neurons can disinhibit corresponding thalamic targets.

This can facilitate activity within cortical networks associated with an intended action.

The process occurs alongside increased inhibition of competing channels within distributed basal ganglia circuits.

Movement Suppression

Increased activity of selected GPi neurons strengthens inhibitory output to downstream targets.

This mechanism contributes to suppression of competing, inappropriate, or unwanted actions.

Effective motor control therefore depends on patterned changes in GPi activity rather than uniform activation or inhibition of the entire nucleus.

Somatotopic Organization

Motor territories within the GPi demonstrate an organized representation of different body regions.

This somatotopic organization reflects corresponding organization within cortical, striatal, and pallidal circuits.

Recognition of these functional territories is important during stereotactic procedures targeting the GPi.

Associative Functions

Not all GPi circuitry is motor.

Associative regions participate in loops involving prefrontal and other association cortices, the striatum, pallidum, thalamus, and cortex.

These circuits contribute to executive and cognitive aspects of action selection and behavioral organization.

Limbic Functions

Ventral pallidal regions participate in limbic basal ganglia circuits associated with motivation, reward, and emotionally influenced behavior.

These circuits interact with the ventral striatum and limbic cortical structures.

The pallidal complex therefore contributes to motor, associative, and limbic processing through anatomically differentiated territories.

Blood Supply

The internal globus pallidus receives blood from deep perforating arteries arising from the anterior circulation.

Important contributions include branches of the anterior choroidal artery and penetrating branches associated with the middle cerebral artery.

The exact distribution is variable, and neighboring arterial territories overlap within the deep gray matter.

Anterior Choroidal Artery

The anterior choroidal artery usually arises from the internal carotid artery.

It supplies portions of the globus pallidus, internal capsule, optic pathways, and other deep structures.

Its relationship to the posteroventral GPi is particularly relevant in stereotactic and functional neurosurgical anatomy.

Lenticulostriate Arteries

The lenticulostriate arteries arise predominantly from the middle cerebral artery and supply portions of the basal ganglia and internal capsule.

They contribute to pallidal vascularization, particularly in territories shared with adjacent deep nuclei.

Occlusion or rupture of these small penetrating vessels can produce focal or combined basal ganglia and capsular lesions.

Venous Drainage

Venous blood from the pallidal region drains into the deep cerebral venous system.

Small veins from the basal ganglia communicate with larger deep veins associated with the ventricular and thalamic regions.

These pathways ultimately contribute to the internal cerebral veins and related deep venous channels.

Clinical Significance

Parkinson Disease

In Parkinson disease, degeneration of dopaminergic neurons in the substantia nigra pars compacta alters striatal signaling and changes the activity of downstream basal ganglia nuclei.

Classically, reduced dopaminergic modulation results in increased inhibitory output from the GPi to the thalamus.

Abnormal firing patterns and network synchronization involving the GPi contribute to bradykinesia, rigidity, and other motor manifestations.

Huntington Disease

In early Huntington disease, degeneration of selected striatal neurons disrupts the indirect pathway.

This can reduce excitatory subthalamic influence on the GPi and decrease inhibitory basal ganglia output.

The resulting alteration of thalamocortical activity contributes to excessive involuntary movements such as chorea.

Dystonia

Abnormal activity within pallidal and broader basal ganglia networks is associated with several forms of dystonia.

Disturbances in firing rate, pattern, synchronization, and network organization can impair the normal selection and suppression of motor programs.

The GPi is consequently an important therapeutic target in selected patients with medically refractory dystonia.

Hemiballismus

Hemiballismus is classically associated with disruption of the contralateral subthalamic nucleus or its connections.

Reduced excitatory drive from the subthalamic nucleus can decrease GPi activity and thereby reduce inhibitory output toward the thalamus.

This disturbance of basal ganglia output can contribute to large-amplitude involuntary movements.

Pallidal Lesions

Structural lesions involving the GPi can alter basal ganglia output and produce abnormalities of movement and muscle tone.

The clinical pattern depends on lesion location, laterality, extent, and involvement of neighboring structures.

Because the internal capsule lies nearby, larger lesions may produce additional motor or sensory deficits unrelated to pallidal dysfunction itself.

Hypoxic and Toxic Injury

The globus pallidus can show characteristic abnormalities in certain forms of hypoxic, toxic, and metabolic injury.

Bilateral pallidal abnormalities may be visible on neuroimaging in selected conditions.

The clinical implications depend on the underlying cause and the involvement of other brain structures.

Deep Brain Stimulation

The GPi is an established target for deep brain stimulation (DBS) in selected movement disorders.

Electrodes are stereotactically positioned within a defined region of the internal pallidum to modify abnormal network activity.

GPi stimulation is used clinically in selected patients with disorders including Parkinson disease and dystonia.

GPi Deep Brain Stimulation Anatomy

Accurate electrode placement requires detailed knowledge of the boundaries of the GPi and neighboring structures.

The external globus pallidus lies laterally, the internal capsule lies medially and posteriorly, and the optic tract lies near the inferior pallidal region.

Stimulation spreading into these neighboring structures can produce effects distinct from stimulation of the intended pallidal target.

Internal Capsule and DBS

The close relationship between the GPi and internal capsule is particularly important during deep brain stimulation.

Electrical current extending into corticospinal or corticobulbar fibers can produce involuntary muscle contractions or other motor effects.

Electrode location and stimulation parameters are therefore adjusted to maximize therapeutic effects while limiting spread to adjacent structures.

Optic Tract Relationship

The optic tract passes close to the inferior aspect of the internal pallidal region.

This relationship provides an important anatomical landmark during stereotactic localization.

Stimulation extending toward the optic tract can produce visual phenomena, emphasizing the need for precise targeting.

Pallidotomy

Pallidotomy is a functional neurosurgical procedure in which a controlled lesion is created within a selected region of the GPi.

The procedure historically played an important role in treating selected movement disorders and remains relevant in particular clinical settings.

Its effects reflect modification of abnormal inhibitory basal ganglia output.

Neuroimaging

The GPi can be identified on high-resolution MRI by its position within the medial portion of the globus pallidus.

Axial and coronal imaging demonstrates its relationships with the GPe, putamen, internal capsule, and surrounding deep structures.

Specialized imaging sequences and stereotactic atlases may be used for functional neurosurgical planning.

Sectional Anatomy

In coronal sections, the GPi appears as the medial portion of the pallidal complex.

From lateral to medial, the principal sequence is putamen → GPe → GPi → internal capsule.

The medullary laminae provide anatomical boundaries between the putamen and pallidal segments and between the two divisions of the globus pallidus.

Functional Relationship with the Thalamus

The relationship between the GPi and thalamus is central to understanding basal ganglia function.

GPi neurons continuously inhibit selected thalamic neurons. Changes in this inhibition regulate the ability of the thalamus to influence cortical activity.

The basal ganglia can therefore control cortical networks through patterned modulation of pallidothalamic inhibition.

Functional Relationship with the Cortex

The GPi does not primarily communicate directly with the cerebral cortex. Instead, its effects on cortical activity are mediated largely through the thalamus.

Cortical information enters basal ganglia circuits through the striatum and subthalamic nucleus, is processed through interconnected nuclei, and reaches the GPi.

GPi output then influences thalamocortical activity, completing major cortico-basal ganglia-thalamo-cortical loops.

Developmental Anatomy

The globus pallidus develops as part of the basal forebrain systems that form the deep nuclei associated with basal ganglia circuitry.

During maturation, pallidal neurons establish organized connections with the striatum, subthalamic nucleus, thalamus, brainstem, and other basal ganglia structures.

The resulting architecture supports the parallel motor, associative, and limbic circuits present in the mature brain.

Anatomical Variation

The size, shape, and precise internal boundaries of the GPi vary among individuals.

Its relationship with the GPe, internal capsule, and optic tract remains sufficiently consistent to provide important landmarks for anatomical and stereotactic localization.

Vascular territories also vary because the small penetrating arteries supplying the pallidum have overlapping distributions.

Functional Importance

The internal globus pallidus is one of the principal structures through which the basal ganglia control activity outside the basal ganglia themselves. Its tonically active GABAergic neurons continuously inhibit thalamic and brainstem targets, while direct, indirect, and hyperdirect pathways dynamically regulate this inhibitory output.

By selectively increasing or decreasing inhibition across different functional channels, the GPi contributes to the facilitation of intended actions and suppression of competing actions. Parallel pallidal territories also participate in associative and limbic functions.

The internal globus pallidus therefore plays major roles in basal ganglia output, movement regulation, action selection, motor suppression, thalamocortical control, and the integration of motor, cognitive, and behavioral information.