Globus Pallidus is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
The globus pallidus (Latin: "pale globe") is a subcortical structure of the basal-ganglia that serves as the primary output nucleus for motor information processed by the striatum. Located medial to the putamen and lateral to the internal capsule, it consists of two functionally distinct segments: the globus pallidus externus (GPe, or lateral segment) and the globus pallidus internus (GPi, or medial segment). [1]
The GPi, together with the substantia-nigra pars reticulata (SNr), provides the final basal ganglia output to the thalamus and brainstem, tonically inhibiting thalamo-cortical activity through GABAergic projections.[2] [3]
The globus pallidus is clinically significant in multiple neurodegenerative diseases and is a major therapeutic target for deep-brain-stimulation (DBS). GPi-DBS is a well-established treatment for parkinsons motor complications, dystonia, and huntington-pathway chorea. [4]
Pathological changes in the globus pallidus occur in Parkinson's Disease, Huntington's Disease, psp, neurodegeneration with brain iron accumulation (NBIA), Wilson's Disease, and other basal ganglia disorders.[1:1] [5]
The globus pallidus is divided into two segments by the internal (medial) medullary lamina: [6]
Globus Pallidus Externus (GPe): [7]
Globus Pallidus Internus (GPi): [8]
Globus pallidus neurons are large, multipolar GABAergic neurons with extensive dendritic arbors. Key features: [9]
The globus pallidus receives its blood supply from the anterior choroidal artery and lenticulostriate arteries (branches of the middle cerebral artery). This vascular territory is susceptible to: [10]
The globus pallidus integrates the output of the direct, indirect, and hyperdirect pathways:[5:1] [11]
In normal function, the dynamic interplay between these pathways allows for the precise selection and execution of desired movements while suppressing unwanted ones. [12]
Recent research has revealed that the GPe is not merely a relay within the indirect pathway but functions as an autonomous pacemaker and integrator:[3:2] [13]
Beyond motor control, the globus pallidus participates in: [14]
In parkinsons, dopamine depletion in the putamen causes a cascade of changes in pallidal activity:[5:2] [15]
This pathological shift in pallidal activity, formalized in the Albin-DeLong model, provides the rationale for therapeutic interventions: [16]
The globus pallidus shows significant pathology in huntington-pathway:[8:1]
In psp, both GPi and GPe show tau] pathology — neurofibrillary tangles, tufted astrocytes, and neuropil threads. Pallidal tau] pathology contributes to the axial rigidity, postural instability, and falls that characterize PSP.
Unlike PD, where pallidal dysfunction results from dopamine depletion, PSP involves direct neuronal loss within the pallidum itself, making the pathophysiology fundamentally different and limiting the efficacy of levodopa therapy.[9:1]
The globus pallidus is the primary site of iron accumulation in NBIA disorders:[10:1]
In Wilson's Disease (hepatolenticular degeneration), copper deposition in the globus pallidus and putamen causes the characteristic "face of the giant panda" sign on T2-weighted MRI (hyperintensity in the tegmentum with hypointense superior colliculi and preserved red nuclei). Pallidal copper deposition contributes to dystonia and parkinsonian features. Copper chelation therapy (penicillamine, trientine) and zinc supplementation can reverse some pallidal changes if initiated early.
In corticobasal-degeneration, the globus pallidus shows asymmetric tau] pathology (astrocytic plaques and ballooned neurons) that correlates with the asymmetric limb rigidity and alien limb phenomena characteristic of this disorder.
Chronic manganese exposure (welding, mining, parenteral nutrition) causes selective pallidal toxicity, producing a parkinsonian syndrome with prominent dystonia. T1-weighted MRI shows bilateral pallidal hyperintensity (due to manganese's paramagnetic properties) — a distinctive pattern that distinguishes manganism from idiopathic PD.
The globus pallidus has distinctive imaging characteristics:[4:2]
T2-weighted MRI: Normally appears hypointense (dark) due to physiological iron deposition that increases with age. Abnormal signal patterns (hyperintensity, the "eye of the tiger") indicate pathological iron deposition or gliosis
T1-weighted MRI: Normally isointense; hyperintensity suggests manganese deposition (hepatic encephalopathy, manganism) or calcification
Quantitative susceptibility mapping (QSM): Quantifies pallidal iron content with high precision; useful for monitoring NBIA disorders, tracking normal aging, and assessing ferroptosis-related neurodegeneration
pet-imaging: GABA-A receptor PET (11C-flumazenil) can quantify pallidal neuronal loss; 18F-FDG PET reveals altered pallidal metabolism in movement disorders. Dopamine D2 receptor PET (11C-raclopride) shows altered pallidal receptor binding in dystonia
Functional MRI: Task-based and resting-state fMRI reveal pallidal activation during motor planning, action selection, and reward-based decision making
DBS electrode imaging: Post-operative CT or MRI verification of DBS lead placement in GPi is critical for optimizing stimulation parameters and clinical outcomes
medium-spiny-neurons
This section links to atlas resources relevant to this brain region.
The study of Globus Pallidus has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Vitek JL, et al. 2012 - Randomized trial of pallidotomy versus medical therapy for Parkinson's Disease. 2012. ↩︎ ↩︎
Parent A, Bhatt M, 2020 - The Globus Pallidus, Handbook of Clinical Neurology. 2020. ↩︎
Abdi A, et al. 2015 - Prototypic and arkypallidal neurons in the dopamine-intact external globus pallidus. 2015. ↩︎ ↩︎ ↩︎
Hallgren B, Sourander P, 1958 - The effect of age on the non-haemin iron in the human brain. 1958. ↩︎ ↩︎ ↩︎
[DeLong MR, 1990 - Primate models of movement disorders of basal ganglia origin](https://doi.org/10.1016/S0166-2236(05). 1990. ↩︎ ↩︎ ↩︎
Mulcahy G, et al. 2023 - GPi deep brain stimulation in Parkinson's Disease: multicenter retrospective study. 2023. ↩︎ ↩︎
GPi-DBS travels to thalamus and STN along physiological pathways, Frontiers in Neuroscience, 2025. 2025. ↩︎ ↩︎
Gonzalez V, et al. 2014 - Deep brain stimulation for Huntington's Disease: long-term results of a prospective open-label study. 2014. ↩︎ ↩︎
[Williams DR, Lees AJ, 2009 - Progressive Supranuclear Palsy: clinicopathological concepts and diagnostic challenges](https://doi.org/10.1016/S1474-4422(09). 2009. ↩︎ ↩︎
Hayflick SJ, et al. 2003 - Genetic, clinical, and radiographic delineation of Hallervorden-Spatz syndrome. 2003. ↩︎ ↩︎
Aylward EH, et al. 2011 - Striatal and pallidal volume in preclinical Huntington's Disease. 2011. ↩︎
Helmich RC, et al. 2021 - GPi-DBS for movement disorders: current evidence and future directions. 2021. ↩︎
BrainSpan Consortium. BrainSpan Atlas of the Developing Human Brain. ↩︎
Litvan I, et al. Movement Disorders. 2011;26(6):1002-1012. 2011. ↩︎