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Nature Oct 2021The cortico-basal ganglia-thalamo-cortical loop is one of the fundamental network motifs in the brain. Revealing its structural and functional organization is critical...
The cortico-basal ganglia-thalamo-cortical loop is one of the fundamental network motifs in the brain. Revealing its structural and functional organization is critical to understanding cognition, sensorimotor behaviour, and the natural history of many neurological and neuropsychiatric disorders. Classically, this network is conceptualized to contain three information channels: motor, limbic and associative. Yet this three-channel view cannot explain the myriad functions of the basal ganglia. We previously subdivided the dorsal striatum into 29 functional domains on the basis of the topography of inputs from the entire cortex. Here we map the multi-synaptic output pathways of these striatal domains through the globus pallidus external part (GPe), substantia nigra reticular part (SNr), thalamic nuclei and cortex. Accordingly, we identify 14 SNr and 36 GPe domains and a direct cortico-SNr projection. The striatonigral direct pathway displays a greater convergence of striatal inputs than the more parallel striatopallidal indirect pathway, although direct and indirect pathways originating from the same striatal domain ultimately converge onto the same postsynaptic SNr neurons. Following the SNr outputs, we delineate six domains in the parafascicular and ventromedial thalamic nuclei. Subsequently, we identify six parallel cortico-basal ganglia-thalamic subnetworks that sequentially transduce specific subsets of cortical information through every elemental node of the cortico-basal ganglia-thalamic loop. Thalamic domains relay this output back to the originating corticostriatal neurons of each subnetwork in a bona fide closed loop.
Topics: Animals; Basal Ganglia; Cerebral Cortex; Male; Mice; Mice, Inbred C57BL; Neural Pathways; Neurons; Thalamus
PubMed: 34616074
DOI: 10.1038/s41586-021-03993-3 -
The New England Journal of Medicine May 2020We report the implantation of patient-derived midbrain dopaminergic progenitor cells, differentiated in vitro from autologous induced pluripotent stem cells (iPSCs), in...
We report the implantation of patient-derived midbrain dopaminergic progenitor cells, differentiated in vitro from autologous induced pluripotent stem cells (iPSCs), in a patient with idiopathic Parkinson's disease. The patient-specific progenitor cells were produced under Good Manufacturing Practice conditions and characterized as having the phenotypic properties of substantia nigra pars compacta neurons; testing in a humanized mouse model (involving peripheral-blood mononuclear cells) indicated an absence of immunogenicity to these cells. The cells were implanted into the putamen (left hemisphere followed by right hemisphere, 6 months apart) of a patient with Parkinson's disease, without the need for immunosuppression. Positron-emission tomography with the use of fluorine-18-L-dihydroxyphenylalanine suggested graft survival. Clinical measures of symptoms of Parkinson's disease after surgery stabilized or improved at 18 to 24 months after implantation. (Funded by the National Institutes of Health and others.).
Topics: Aged; Animals; Basal Ganglia; Cell Differentiation; Disease Models, Animal; Dopaminergic Neurons; Follow-Up Studies; Humans; Induced Pluripotent Stem Cells; Male; Mice; Mice, SCID; Parkinson Disease; Pars Compacta; Positron-Emission Tomography; Putamen; Tomography, X-Ray Computed; Transplantation, Autologous; Transplantation, Homologous
PubMed: 32402162
DOI: 10.1056/NEJMoa1915872 -
Nature Reviews. Neuroscience Nov 2019Midbrain dopamine signals are widely thought to report reward prediction errors that drive learning in the basal ganglia. However, dopamine has also been implicated in... (Review)
Review
Midbrain dopamine signals are widely thought to report reward prediction errors that drive learning in the basal ganglia. However, dopamine has also been implicated in various probabilistic computations, such as encoding uncertainty and controlling exploration. Here, we show how these different facets of dopamine signalling can be brought together under a common reinforcement learning framework. The key idea is that multiple sources of uncertainty impinge on reinforcement learning computations: uncertainty about the state of the environment, the parameters of the value function and the optimal action policy. Each of these sources plays a distinct role in the prefrontal cortex-basal ganglia circuit for reinforcement learning and is ultimately reflected in dopamine activity. The view that dopamine plays a central role in the encoding and updating of beliefs brings the classical prediction error theory into alignment with more recent theories of Bayesian reinforcement learning.
Topics: Animals; Basal Ganglia; Dopamine; Humans; Learning; Nerve Net; Prefrontal Cortex
PubMed: 31570826
DOI: 10.1038/s41583-019-0220-7 -
Frontiers in Neural Circuits 2021A biological reward system is integral to all animal life and humans are no exception. For millennia individuals have investigated this system and its influences on... (Review)
Review
A biological reward system is integral to all animal life and humans are no exception. For millennia individuals have investigated this system and its influences on human behavior. In the modern day, with the US facing an ongoing epidemic of substance use without an effective treatment, these investigations are of paramount importance. It is well known that basal ganglia contribute to rewards and are involved in learning, approach behavior, economic choices, and positive emotions. This review aims to elucidate the physiological role of striatonigrostriatal (SNS) spirals, as part of basal ganglia circuits, in this reward system and their pathophysiological role in perpetuating addiction. Additionally, the main functions of neurotransmitters such as dopamine and glutamate and their receptors in SNS circuits will be summarized. With this information, the claim that SNS spirals are crucial intermediaries in the shift from goal-directed behavior to habitual behavior will be supported, making this circuit a viable target for potential therapeutic intervention in those with substance use disorders.
Topics: Animals; Basal Ganglia; Behavior, Addictive; Dopamine; Humans; Reward; Substance-Related Disorders
PubMed: 34955762
DOI: 10.3389/fncir.2021.803501 -
The Lancet. Child & Adolescent Health Dec 2019The diagnosis and management of movement disorders in children can be improved by understanding the pathways, neurons, ion channels, and receptors involved in motor... (Review)
Review
The diagnosis and management of movement disorders in children can be improved by understanding the pathways, neurons, ion channels, and receptors involved in motor learning and control. In this Review, we use a localisation approach to examine the anatomy, physiology, and circuitry of the basal ganglia and highlight the mechanisms that underlie some of the major movement disorders in children. We review the connections between the basal ganglia and the thalamus and cortex, address the basic clinical definitions of movement disorders, and then place diseases within an anatomical or physiological framework that highlights basal ganglia function. We discuss how new pharmacological, behavioural, and electrophysiological approaches might benefit children with movement disorders by modifying synaptic function. A better understanding of the mechanisms underlying movement disorders allows improved diagnostic and treatment decisions.
Topics: Adolescent; Basal Ganglia; Cerebral Cortex; Child; Cognitive Behavioral Therapy; Dopamine; Electrophysiological Phenomena; Humans; Motor Neurons; Movement Disorders; Synapses; Thalamus; Young Adult
PubMed: 31653548
DOI: 10.1016/S2352-4642(19)30330-X -
Arquivos de Neuro-psiquiatria Dec 2020
Topics: Basal Ganglia; Basal Ganglia Diseases; Humans; Parkinsonian Disorders
PubMed: 33263640
DOI: 10.1590/0004-282X20200103 -
Brain and Language Aug 2021Dopamine, the main catecholamine neurotransmitter in the brain, is predominately produced in the basal ganglia and released to various brain regions including the...
Dopamine, the main catecholamine neurotransmitter in the brain, is predominately produced in the basal ganglia and released to various brain regions including the frontal cortex, midbrain and brainstem. Dopamine's effects are widespread and include modulation of a number of voluntary and innate behaviors. Vigilant regulation and modulation of dopamine levels throughout the brain is imperative for proper execution of motor behaviors, in particular speech and other types of vocalizations. While dopamine's role in motor circuitry is widely accepted, its unique function in normal and abnormal speech production is not fully understood. In this perspective, we first review the role of dopaminergic circuits in vocal production. We then discuss and propose the conceivable involvement of astrocytes, the numerous star-shaped glia cells of the brain, in the dopaminergic network modulating normal and abnormal vocal productions.
Topics: Astrocytes; Basal Ganglia; Brain; Dopamine; Humans; Speech
PubMed: 34098250
DOI: 10.1016/j.bandl.2021.104970 -
Medicina (Kaunas, Lithuania) May 2023Perivascular spaces (PVS) and their enlargement (EPVS) have been gaining interest as EPVS can be visualized non-invasively by magnetic resonance imaging (MRI) when... (Review)
Review
Perivascular spaces (PVS) and their enlargement (EPVS) have been gaining interest as EPVS can be visualized non-invasively by magnetic resonance imaging (MRI) when viewing T-2-weighted images. EPVS are most commonly observed in the regions of the basal ganglia and the centrum semiovale; however, they have also been identified in the frontal cortex and hippocampal regions. EPVS are known to be increased in aging and hypertension, and are considered to be a biomarker of cerebral small vessel disease (SVD). Interest in EPVS has been significantly increased because these PVS are now considered to be an essential conduit necessary for the glymphatic pathway to provide the necessary efflux of metabolic waste. Metabolic waste includes misfolded proteins of amyloid beta and tau that are known to accumulate in late-onset Alzheimer's disease (LOAD) within the interstitial fluid that is delivered to the subarachnoid space and eventually the cerebral spinal fluid (CSF). The CSF acts as a sink for accumulating neurotoxicities and allows clinical screening to potentially detect if LOAD may be developing early on in its clinical progression via spinal fluid examination. EPVS are thought to occur by obstruction of the PVS that associates with excessive neuroinflammation, oxidative stress, and vascular stiffening that impairs flow due to a dampening of the arterial and arteriolar pulsatility that aids in the convective flow of the metabolic debris within the glymphatic effluxing system. Additionally, increased EPVS has also been associated with Parkinson's disease and non-age-related multiple sclerosis (MS).
Topics: Humans; Amyloid beta-Peptides; Magnetic Resonance Imaging; Aging; Basal Ganglia; Arteries
PubMed: 37241149
DOI: 10.3390/medicina59050917 -
Social Cognitive and Affective... Jul 2020The basal ganglia (BG) and the cerebellum historically have been relegated to a functional role in producing or modulating motor output. Recent research, however, has... (Review)
Review
The basal ganglia (BG) and the cerebellum historically have been relegated to a functional role in producing or modulating motor output. Recent research, however, has emphasized the importance of these subcortical structures in multiple functional domains, including affective processes such as emotion recognition, subjective feeling elicitation and reward valuation. The pathways through the thalamus that connect the BG and cerebellum directly to each other and with extensive regions of the cortex provide a structural basis for their combined influence on limbic function. By regulating cortical oscillations to guide learning and strengthening rewarded behaviors or thought patterns to achieve a desired goal state, these regions can shape the way an individual processes emotional stimuli. This review will discuss the basic structure and function of the BG and cerebellum and propose an updated view of their functional role in human affective processing.
Topics: Basal Ganglia; Cerebellum; Emotions; Humans; Learning; Motivation; Neural Pathways; Neuroimaging
PubMed: 32507876
DOI: 10.1093/scan/nsaa076 -
Neurology India 2022Basal ganglia encephalitis is a part of the spectrum of autoimmune basal ganglia disorders. We are reporting a child who had a fever with focal seizures followed by...
Basal ganglia encephalitis is a part of the spectrum of autoimmune basal ganglia disorders. We are reporting a child who had a fever with focal seizures followed by behavioral problems, rigidity, bradykinesia, and dystonia. His parkinsonism-like features were increasing day by day up to the level that the child was non-ambulatory. His initial Magnetic Resonance Imaging (MRI) of the brain showed asymmetrical T2 hyperintensities involving both the caudate nuclei and putamina. Later, with progressive symptoms, repeat MRI revealed a swelling and symmetrical signal change in both the caudate nuclei and putamina in the form of T2 and Fluid-attenuated inversion recovery (FLAIR) hyperintensities. In addition, there was T2 hyperintensity involving bilateral substantia nigra. Serum basal ganglia antibody, Leptospira Immunoglobulin M (IgM) antibody was positive, and Cerebrospinal Fluid (CSF) oligoclonal band was positive. So, the child was diagnosed with post-leptospirosis autoimmune basal ganglia encephalitis. He was managed with immunomodulatory agents and significant improvement in the symptoms with mild residual extrapyramidal symptoms were noted.
Topics: Child; Male; Humans; Encephalitis; Basal Ganglia; Basal Ganglia Diseases; Magnetic Resonance Imaging; Leptospirosis
PubMed: 36352619
DOI: 10.4103/0028-3886.359156