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Journal of Neuroscience Research Jul 2022Complex regional pain syndrome (CRPS) is a painful condition commonly accompanied by movement disturbances and often affects the upper limbs. The basal ganglia motor...
Complex regional pain syndrome (CRPS) is a painful condition commonly accompanied by movement disturbances and often affects the upper limbs. The basal ganglia motor loop is central to movement, however, non-motor basal ganglia loops are involved in pain, sensory integration, visual processing, cognition, and emotion. Systematic evaluation of each basal ganglia functional loop and its relation to motor and non-motor disturbances in CRPS has not been investigated. We recruited 15 upper limb CRPS and 45 matched healthy control subjects. Using functional magnetic resonance imaging, infraslow oscillations (ISO) and resting-state functional connectivity in motor and non-motor basal ganglia loops were investigated using putamen and caudate seeds. Compared to controls, CRPS subjects displayed increased ISO power in the putamen contralateral to the CRPS affected limb, specifically, in contralateral putamen areas representing the supplementary motor area hand, motor hand, and motor tongue. Furthermore, compared to controls, CRPS subjects displayed increased resting connectivity between these putaminal areas as well as from the caudate body to cortical areas such as the primary motor cortex, supplementary and cingulate motor areas, parietal association areas, and the orbitofrontal cortex. These findings demonstrate changes in basal ganglia loop function in CRPS subjects and may underpin motor disturbances of CRPS.
Topics: Basal Ganglia; Complex Regional Pain Syndromes; Hand; Humans; Magnetic Resonance Imaging; Movement
PubMed: 35441738
DOI: 10.1002/jnr.25057 -
Parkinsonism & Related Disorders Feb 2019Drawing on the seminal work of DeLong, Albin, and Young, we have now entered an era of basal ganglia neuromodulation. Understanding, re-evaluating, and leveraging the... (Review)
Review
INTRODUCTION
Drawing on the seminal work of DeLong, Albin, and Young, we have now entered an era of basal ganglia neuromodulation. Understanding, re-evaluating, and leveraging the lessons learned from neuromodulation will be crucial to facilitate an increased and improved application of neuromodulation in human disease.
METHODS
We will focus on deep brain stimulation (DBS) - the most common form of basal ganglia neuromodulation - however, similar principles can apply to other neuromodulation modalities. We start with a brief review of DBS for Parkinson's disease, essential tremor, dystonia, and Tourette syndrome. We then review hallmark studies on basal ganglia circuits and electrophysiology resulting from decades of experience in neuromodulation. The organization and content of this paper follow Dr. Okun's Lecture from the 2018 Parkinsonism and Related Disorders World Congress.
RESULTS
Information gained from neuromodulation has led to an expansion of the basal ganglia rate model, an enhanced understanding of nuclei dynamics, an emerging focus on pathological oscillations, a revision of the tripartite division of the basal ganglia, and a redirected focus toward individualized symptom-specific stimulation. Though there have been many limitations of the basal ganglia "box model," the construct provided the necessary foundation to advance the field. We now understand that information in the basal ganglia is encoded through complex neural responses that can be reliably measured and used to infer disease states for clinical translation.
CONCLUSIONS
Our deepened understanding of basal ganglia physiology will drive new neuromodulation strategies such as adaptive DBS or cell-specific neuromodulation through the use of optogenetics.
Topics: Animals; Basal Ganglia; Deep Brain Stimulation; Humans; Movement Disorders; Neural Pathways
PubMed: 30658883
DOI: 10.1016/j.parkreldis.2019.01.009 -
The European Journal of Neuroscience May 2016The external globus pallidus (GPe) of the basal ganglia is in a unique and powerful position to influence processing of motor information by virtue of its widespread... (Review)
Review
The external globus pallidus (GPe) of the basal ganglia is in a unique and powerful position to influence processing of motor information by virtue of its widespread projections to all basal ganglia nuclei. Despite the clinical importance of the GPe in common motor disorders such as Parkinson's disease, there is only limited information about its cellular composition and organizational principles. In this review, recent advances in the understanding of the diversity in the molecular profile, anatomy, physiology and corresponding behaviour during movement of GPe neurons are described. Importantly, this study attempts to build consensus and highlight commonalities of the cellular classification based on existing but contentious literature. Additionally, an analysis of the literature concerning the intricate reciprocal loops formed between the GPe and major synaptic partners, including both the striatum and the subthalamic nucleus, is provided. In conclusion, the GPe has emerged as a crucial node in the basal ganglia macrocircuit. While subtleties in the cellular makeup and synaptic connection of the GPe create new challenges, modern research tools have shown promise in untangling such complexity, and will provide better understanding of the roles of the GPe in encoding movements and their associated pathologies.
Topics: Animals; Basal Ganglia; Brain Diseases; Globus Pallidus; Humans; Movement; Neural Pathways; Neurons; Subthalamic Nucleus
PubMed: 26841063
DOI: 10.1111/ejn.13196 -
Journal of Neural Transmission (Vienna,... Mar 2018Studies in non-human primates (NHPs) have led to major advances in our understanding of the function of the basal ganglia and of the pathophysiologic mechanisms of... (Review)
Review
Studies in non-human primates (NHPs) have led to major advances in our understanding of the function of the basal ganglia and of the pathophysiologic mechanisms of hypokinetic movement disorders such as Parkinson's disease and hyperkinetic disorders such as chorea and dystonia. Since the brains of NHPs are anatomically very close to those of humans, disease states and the effects of medical and surgical approaches, such as deep brain stimulation (DBS), can be more faithfully modeled in NHPs than in other species. According to the current model of the basal ganglia circuitry, which was strongly influenced by studies in NHPs, the basal ganglia are viewed as components of segregated networks that emanate from specific cortical areas, traverse the basal ganglia, and ventral thalamus, and return to the frontal cortex. Based on the presumed functional domains of the different cortical areas involved, these networks are designated as 'motor', 'oculomotor', 'associative' and 'limbic' circuits. The functions of these networks are strongly modulated by the release of dopamine in the striatum. Striatal dopamine release alters the activity of striatal projection neurons which, in turn, influences the (inhibitory) basal ganglia output. In parkinsonism, the loss of striatal dopamine results in the emergence of oscillatory burst patterns of firing of basal ganglia output neurons, increased synchrony of the discharge of neighboring basal ganglia neurons, and an overall increase in basal ganglia output. The relevance of these findings is supported by the demonstration, in NHP models of parkinsonism, of the antiparkinsonian effects of inactivation of the motor circuit at the level of the subthalamic nucleus, one of the major components of the basal ganglia. This finding also contributed strongly to the revival of the use of surgical interventions to treat patients with Parkinson's disease. While ablative procedures were first used for this purpose, they have now been largely replaced by DBS of the subthalamic nucleus or internal pallidal segment. These procedures are not only effective in the treatment of parkinsonism, but also in the treatment of hyperkinetic conditions (such as chorea or dystonia) which result from pathophysiologic changes different from those underlying Parkinson's disease. Thus, these interventions probably do not counteract specific aspects of the pathophysiology of movement disorders, but non-specifically remove the influence of the different types of disruptive basal ganglia output from the relatively intact portions of the motor circuitry downstream from the basal ganglia. Knowledge gained from studies in NHPs remains critical for our understanding of the pathophysiology of movement disorders, of the effects of DBS on brain network activity, and the development of better treatments for patients with movement disorders and other neurologic or psychiatric conditions.
Topics: Animals; Basal Ganglia; Brain; Deep Brain Stimulation; Disease Models, Animal; Movement Disorders; Neural Pathways; Primates
PubMed: 28601961
DOI: 10.1007/s00702-017-1736-5 -
Movement Disorders : Official Journal... May 2018In this Scientific Perspectives we first review the recent advances in our understanding of the functional architecture of basal ganglia circuits. Then we argue that... (Review)
Review
In this Scientific Perspectives we first review the recent advances in our understanding of the functional architecture of basal ganglia circuits. Then we argue that these data can best be explained by a model in which basal ganglia act to control the gain of movement kinematics to shape performance based on prior experience, which we refer to as a history-dependent gain computation. Finally, we discuss how insights from the history-dependent gain model might translate from the bench to the bedside, primarily the implications for the design of adaptive deep brain stimulation. Thus, we explicate the key empirical and conceptual support for a normative, computational model with substantial explanatory power for the broad role of basal ganglia circuits in health and disease. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Topics: Animals; Basal Ganglia; Biomechanical Phenomena; Computer Simulation; Humans; Models, Neurological; Movement; Neural Pathways
PubMed: 29575303
DOI: 10.1002/mds.27321 -
Brain : a Journal of Neurology Jul 2015The basal ganglia control body movements, value processing and decision-making. Many studies have shown that the inputs and outputs of each basal ganglia structure are... (Review)
Review
The basal ganglia control body movements, value processing and decision-making. Many studies have shown that the inputs and outputs of each basal ganglia structure are topographically organized, which suggests that the basal ganglia consist of separate circuits that serve distinct functions. A notable example is the circuits that originate from the rostral (head) and caudal (tail) regions of the caudate nucleus, both of which target the superior colliculus. These two caudate regions encode the reward values of visual objects differently: flexible (short-term) values by the caudate head and stable (long-term) values by the caudate tail. These value signals in the caudate guide the orienting of gaze differently: voluntary saccades by the caudate head circuit and automatic saccades by the caudate tail circuit. Moreover, separate groups of dopamine neurons innervate the caudate head and tail and may selectively guide the flexible and stable learning/memory in the caudate regions. Studies focusing on manual handling of objects also suggest that rostrocaudally separated circuits in the basal ganglia control the action differently. These results suggest that the basal ganglia contain parallel circuits for two steps of goal-directed behaviour: finding valuable objects and manipulating the valuable objects. These parallel circuits may underlie voluntary behaviour and automatic skills, enabling animals (including humans) to adapt to both volatile and stable environments. This understanding of the functions and mechanisms of the basal ganglia parallel circuits may inform the differential diagnosis and treatment of basal ganglia disorders.
Topics: Animals; Basal Ganglia; Behavior; Decision Making; Humans; Neural Pathways; Reward
PubMed: 25981958
DOI: 10.1093/brain/awv134 -
Neuroradiology Dec 2020The basal ganglia and thalami are paired deep grey matter structures with extensive metabolic activity that renders them susceptible to injury by various diseases. Most... (Review)
Review
The basal ganglia and thalami are paired deep grey matter structures with extensive metabolic activity that renders them susceptible to injury by various diseases. Most pathological processes lead to bilateral lesions, which may be symmetric or asymmetric, frequently showing characteristic patterns on imaging studies. In this comprehensive pictorial review, the most common and/or typical genetic, acquired metabolic/toxic, infectious, inflammatory, vascular and neoplastic pathologies affecting the central grey matter are subdivided according to the preferential location of the lesions: in the basal ganglia, in the thalami or both. The characteristic imaging findings are described with emphasis on the differential diagnosis and clinical context.
Topics: Basal Ganglia; Brain Diseases; Diagnosis, Differential; Gray Matter; Humans; Thalamus
PubMed: 32761278
DOI: 10.1007/s00234-020-02511-y -
Scientific Reports Jun 2021The experimental study of the human brain has important restrictions, particularly in the case of basal ganglia, subcortical centers whose activity can be recorded with...
The experimental study of the human brain has important restrictions, particularly in the case of basal ganglia, subcortical centers whose activity can be recorded with fMRI methods but cannot be directly modified. Similar restrictions occur in other complex systems such as those studied by Earth system science. The present work studied the cause/effect relationships between human basal ganglia with recently introduced methods to study climate dynamics. Data showed an exhaustive (identifying basal ganglia interactions regardless of their linear, non-linear or complex nature) and selective (avoiding spurious relationships) view of basal ganglia activity, showing a fast functional reconfiguration of their main centers during the execution of voluntary motor tasks. The methodology used here offers a novel view of the human basal ganglia which expands the perspective provided by the classical basal ganglia model and may help to understand BG activity under normal and pathological conditions.
Topics: Adult; Aged; Algorithms; Basal Ganglia; Brain Mapping; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Models, Neurological; Neural Pathways; Young Adult
PubMed: 34155321
DOI: 10.1038/s41598-021-92490-8 -
The Neuroscientist : a Review Journal... Aug 2019The basal ganglia are an intricately connected assembly of subcortical nuclei, forming the core of an adaptive network connecting cortical and thalamic circuits. For... (Review)
Review
The basal ganglia are an intricately connected assembly of subcortical nuclei, forming the core of an adaptive network connecting cortical and thalamic circuits. For nearly three decades, researchers and medical practitioners have conceptualized how the basal ganglia circuit works, and how its pathology underlies motor disorders such as Parkinson's and Huntington's diseases, using what is often referred to as the "box-and-arrow model": a circuit diagram showing the broad strokes of basal ganglia connectivity and the pathological increases and decreases in the weights of specific connections that occur in disease. While this model still has great utility and has led to groundbreaking strategies to treat motor disorders, our evolving knowledge of basal ganglia function has made it clear that this classic model has several shortcomings that severely limit its predictive and descriptive abilities. In this review, we will focus on the striatum, the main input nucleus of the basal ganglia. We describe recent advances in our understanding of the rich microcircuitry and plastic capabilities of the striatum, factors not captured by the original box-and-arrow model, and provide examples of how such advances inform our current understanding of the circuit pathologies underlying motor disorders.
Topics: Acetylcholine; Animals; Basal Ganglia; Corpus Striatum; Dopamine; GABAergic Neurons; Humans; Interneurons; Models, Neurological; Movement Disorders; Neural Pathways; Neuronal Plasticity
PubMed: 30379121
DOI: 10.1177/1073858418807887 -
Human Brain Mapping Feb 2022Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by both motor and non-motor symptoms. A convergent pathophysiological hallmark of PD is...
Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by both motor and non-motor symptoms. A convergent pathophysiological hallmark of PD is an early selective vulnerability within the basal ganglia circuit. However, the causal interactions between basal ganglia atrophy and progressive structural network alterations in PD remain unaddressed. Here, we adopted voxel-based morphometry method to measure gray matter (GM) volume for each participant (n = 84 PD patients and n = 70 matched healthy controls). Patients were first divided into three stages according to the Hoehn and Yahr (H&Y) and the Part III of Unified Parkinson's Disease Rating Scale scores respectively to analyze the stage-specific GM atrophy patterns. Then, the modulation of early caudate atrophy over other brain structures was evaluated using the whole-brain voxel-wise and region-of-interest-wise causal structural covariance network approaches. We found that GM atrophy progressively expands from the basal ganglia to the angular gyrus, temporal areas, and eventually spreads through the subcortical-cortical networks as PD progresses. Notably, we identified a shared caudate-associated degeneration network including the basal ganglia, thalamus, cerebellum, sensorimotor cortex, and cortical association areas with the PD progressive factors. These findings suggest that the early structural vulnerability of basal ganglia in PD may play a pivotal role in the modulation of motor and non-motor circuits at the structural level. Our work provides evidence for a novel mechanism of network degeneration that underlies the pathology of PD and may have potential clinical applications in the development of early predictors of PD onset and progress.
Topics: Adult; Aged; Atrophy; Basal Ganglia; Female; Gray Matter; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Nerve Net; Parkinson Disease
PubMed: 34792836
DOI: 10.1002/hbm.25715