The centromedian nucleus: Anatomy, physiology, and clinical implications

doi:10.1016/j.jocn.2019.01.050

Journal of Clinical Neuroscience

Volume 63, May 2019, Pages 1-7

https://doi.org/10.1016/j.jocn.2019.01.050 Get rights and content

Highlights

•
The CM is located within thalamic IML and has diverse functional connectivity.
•
The CM participates in sensorimotor coordination, cognition, and pain processing.
•
The CM is a potential DBS target for movement disorders, epilepsy, pain, and coma.

Abstract

Of all the truncothalamic nuclei, the centromedian-parafascicular nuclei complex (CM-Pf) is the largest and is considered the prototypic thalamic projection system. Located among the caudal intralaminar thalamic nuclei, the CM-Pf been described by Jones as “the forgotten components of the great loop of connections joining the cerebral cortex via the basal ganglia”. The CM, located lateral relative to the Pf, is a major source of direct input to the striatum and also has connections to other, distinct region of the basal ganglia as well as the brainstem and cortex. Functionally, the CM participates in sensorimotor coordination, cognition (e.g. attention, arousal), and pain processing. The role of CM as ‘gate control’ function by propagating only salient stimuli during attention-demanding tasks has been proposed. Given its rich connectivity and diverse physiologic role, recent studies have explored the CM as potential target for neuromodulation therapy for Tourette syndrome, Parkinson’s disease, generalized epilepsy, intractable neuropathic pain, and in restoring consciousness. This comprehensive review summarizes the structural and functional anatomy of the CM and its physiologic role with a focus on clinical implications.

Introduction

The centromedian-parafascicular nuclei complex (CM-Pf) is located among the caudal intralaminar thalamic nuclei and has been described by Jones as “the forgotten components of the great loop of connections joining the cerebral cortex via the basal ganglia” [1], [2]. Functionally, the CM participates in sensorimotor coordination, cognition (e.g. attention, arousal), and pain processing. Given its rich connectivity and diverse physiologic role, recent studies have explored the CM as potential target for neuromodulation therapy for different neurobehavioral illness. Therefore, in light of recent findings, the objective of this review is to describe the structural and functional anatomy of the CM and its physiologic role with a focus on clinical implications.

Section snippets

Structural and functional anatomy

Of all the truncothalamic nuclei, CM-Pf is the largest cell complex and is considered the prototypic thalamic projection system. The CM-Pf complex is a spheroid-shaped structure approximately 1 cm in diameter that lies within the internal medullary lamina (IML) of the thalamus, a rostrally bifurcating intra-thalamic tract that reciprocally transmits thalamocortical information [2]. Within the IML are two groups of nuclei, of which the caudal group contains the CM (Fig. 1, Fig. 2). Medially

Role in sensorimotor function

The CM nucleus is believed to play a significant role in control of sensorimotor function via the thalamostriatal circuit. Based on rodent studies, the thalamostriatal input, of which the CM is a primary component, modulates the activity of medium spiny neurons (MSN), the principle striatopallidal and striatonigral output neurons of the striatum [25], [26]. The precise mechanism behind this modulation and its functional relevance continues to evolve [27]. In primate studies, tonically active

Clinical implications

The CM has been the target for deep brain stimulation (DBS) for a variety of disorders. A systematic review of this topic yielded relevant reviews, randomized controlled trials, cohort series, and case reports. Results from these studies are summarized below.

Conclusions

The CM is a small structure within the heart of the thalamus, yet it has diverse functional connectivity. Chief among its known functions include facilitation of sensorimotor learning via its relationship with the basal ganglia, arousal and vigilance via its direct and indirect diffuse connectivity with the cortex, and processing of affective pain via its involvement in the paleospinothalamic network. Consequently, CM DBS has a wide range of known and potential clinical implications including

Funding

This research received no specific grant from funding agencies in the public, commercial or not-for-profit sectors.

Competing interests

None.

Author contributions

Conception and design: AI, SP. Acquisition of data: AI. Drafting the article: AI. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: AI. Administrative/technical/material support: AR, KOR, SP. Study supervision: AR, KOR, SP.

Data sharing

N/A.

Conflicts of interest

None.

Acknowledgements

N/A.

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Review articleThe centromedian nucleus: Anatomy, physiology, and clinical implications

Highlights

Abstract

Introduction

Section snippets

Structural and functional anatomy

Role in sensorimotor function

Clinical implications

Conclusions

Funding

Competing interests

Author contributions

Data sharing

Conflicts of interest

Acknowledgements

Brain Res Rev

Brain Res Bull

Trends Neurosci

Neuron

Neuron

Neuroscience

Neuroscience

Neurosci Lett

Trends Neurosci

Cortex

Biol Psychiatry

J Am Acad Child Adolesc Psychiatry

Neuromodulation

Parkinsonism Relat Disord

Brain Res Bull

Epilepsia

Electroencephalogr Clin Neurophysiol

Arch Med Res

Neurosurg Clin N Am

Ann Fr Anesth Reanim

Electroencephalogr Clin Neurophysiol

Electroencephalogr Clin Neurophysiol

Arch Phys Med Rehabil

Morphology, nomenclature and connections of the thalamus and basal ganglia

Nigral and pallidal inputs to functionally segregated thalamostriatal neurons in the centromedian/parafascicular intralaminar nuclear complex in monkey

J Comp Neurol

A note on the centre médian nucleus of luys

J Anat

The subthalamic nucleus and Jules Bernard Luys (1828–97)

J Neurol Neurosurg Psychiatry

Center median-parafascicular complex and pain control: Review from a neurosurgical perspective

Stereotact Funct Neurosurg

The human central nervous system

Intralaminar and medial thalamic influence on cortical synchrony, information transmission and cognition

Front Syst Neurosci

Organization of the diffuse thalamic projection system

J Neurophysiol

Effects of stimulation of the centromedian nucleus of the thalamus on the activity of striatal cells in awake rhesus monkeys

Eur J Neurosci

Single-axon tracing and three-dimensional reconstruction of centre médian-parafascicular thalamic neurons in primates

J Comp Neurol

Differential synaptic innervation of striatofugal neurones projecting to the internal or external segments of the globus pallidus by thalamic afferents in the squirrel monkey

J Comp Neurol

The midline and intralaminar thalamic nuclei: anatomic and functional specificity and implications in neurologic disease

Neurology

The intralaminar and midline nuclei of the thalamus. Anatomical and functional evidence for participation in processes of arousal and awareness

Brain Res Brain Res Rev

Efferent connections of the centromedian and parafascicular thalamic nuclei in the squirrel monkey: a light and electron microscopic study of the thalamostriatal projection in relation to striatal heterogeneity

J Comp Neurol

Topographical organization of the pedunculopontine nucleus

Front Neuroanat

The pedunculopontine tegmental nucleus as a motor and cognitive interface between the cerebellum and basal ganglia

Front Neuroanat

Neocortical and caudate projections of intralaminar thalamic neurons and their synaptic excitation from midbrain reticular core

J Neurophysiol

The thalamostriatal system in normal and diseased states

Front Syst Neurosci

Tourette’s syndrome and deep brain stimulation

J Neurol Neurosurg Psychiatry

Thalamo–cortical network underlying deep brain stimulation of centromedian thalamic nuclei in intractable epilepsy: a multimodal imaging analysis

Neuropsychiatr Dis Treat

Coordinated expression of dopamine receptors in neostriatal medium spiny neurons

J Neurosci

Corticostriatal and thalamostriatal synapses have distinctive properties

J Neurosci

Review article
The centromedian nucleus: Anatomy, physiology, and clinical implications