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Neural Plasticity 2003This paper briefly reviews the functional anatomy of the basal ganglia and their relationships with the thalamocortical system. The basal ganglia, including the... (Review)
Review
This paper briefly reviews the functional anatomy of the basal ganglia and their relationships with the thalamocortical system. The basal ganglia, including the striatum, pallidum, subthalamic nucleus, and substantia nigra, are involved in a number of parallel, functionally segregated cortical-subcortical circuits. These circuits support a wide range of sensorimotor, cognitive and emotional-motivational brain functions. A main role of the basal ganglia is the learning and selection of the most appropriate motor or behavioral programs. The internal functional organization of the basal ganglia is very well suited for such selection mechanisms, both in development and in adulthood. The question of whether clumsiness may be, at least in part, attributed to dysfunction of the basal ganglia is discussed in the context of the differential, complementary, or interactive roles of the basal ganglia and the cerebellum in the development of motor control.
Topics: Animals; Basal Ganglia; Cerebellum; Cerebral Cortex; Dopamine; Humans; Learning; Limbic System; Motor Activity; Motor Skills Disorders; Movement; Neural Pathways; Psychomotor Performance; Substantia Nigra; Subthalamic Nucleus; Thalamus
PubMed: 14640312
DOI: 10.1155/NP.2003.107 -
Journal of Parkinson's Disease 2017Subthalamic Nucleus Deep Brain Stimulation (STN DBS) is a well-established and effective treatment modality for selected patients with Parkinson's disease (PD). Since... (Review)
Review
Subthalamic Nucleus Deep Brain Stimulation (STN DBS) is a well-established and effective treatment modality for selected patients with Parkinson's disease (PD). Since its advent, systematic exploration of the effect of stimulation parameters including the stimulation intensity, frequency, and pulse width have been carried out to establish optimal therapeutic ranges. This review examines published data on these stimulation parameters in terms of efficacy of treatment and adverse effects. Altering stimulation intensity is the mainstay of titration in DBS programming via alterations in voltage or current settings, and is characterised by a lower efficacy threshold and a higher side effect threshold which define the therapeutic window. In addition, much work has been done in exploring the effects of frequency modulation, which may help patients with gait freezing and other axial symptoms. However, there is a paucity of data on the use of ultra-short pulse width settings which are now possible with technological advances. We also discuss current evidence for the use of novel programming techniques including directional and adaptive stimulation, and highlight areas for future research.
Topics: Deep Brain Stimulation; Humans; Parkinson Disease; Subthalamic Nucleus; Treatment Outcome
PubMed: 28505983
DOI: 10.3233/JPD-171077 -
The Journal of Neuroscience : the... Jun 2022The cortico-basal ganglia circuit is needed to suppress prepotent actions and to facilitate controlled behavior. Under conditions of response conflict, the frontal...
The cortico-basal ganglia circuit is needed to suppress prepotent actions and to facilitate controlled behavior. Under conditions of response conflict, the frontal cortex and subthalamic nucleus (STN) exhibit increased spiking and theta band power, which are linked to adaptive regulation of behavioral output. The electrophysiological mechanisms underlying these neural signatures of impulse control remain poorly understood. To address this lacuna, we constructed a novel large-scale, biophysically principled model of the subthalamopallidal (STN-globus pallidus externus) network and examined the mechanisms that modulate theta power and spiking in response to cortical input. Simulations confirmed that theta power does not emerge from intrinsic network dynamics but is robustly elicited in response to cortical input as burst events representing action selection dynamics. Rhythmic burst events of multiple cortical populations, representing a state of conflict where cortical motor plans vacillate in the theta range, led to prolonged STN theta and increased spiking, consistent with empirical literature. Notably, theta band signaling required NMDA, but not AMPA, currents, which were in turn related to a triphasic STN response characterized by spiking, silence, and bursting periods. Finally, theta band resonance was also strongly modulated by architectural connectivity, with maximal theta arising when multiple cortical populations project to individual STN "conflict detector" units because of an NMDA-dependent supralinear response. Our results provide insights into the biophysical principles and architectural constraints that give rise to STN dynamics during response conflict, and how their disruption can lead to impulsivity and compulsivity. The subthalamic nucleus exhibits theta band power modulation related to cognitive control over motor actions during conditions of response conflict. However, the mechanisms of such dynamics are not understood. Here we developed a novel biophysically detailed and data-constrained large-scale model of the subthalamopallidal network, and examined the impacts of cellular and network architectural properties that give rise to theta dynamics. Our investigations implicate an important role for NMDA receptors and cortico-subthalamic nucleus topographical connectivities in theta power modulation.
Topics: Basal Ganglia; Globus Pallidus; Motor Cortex; N-Methylaspartate; Subthalamic Nucleus
PubMed: 35477903
DOI: 10.1523/JNEUROSCI.2433-19.2022 -
Brain Structure & Function Sep 2023The Subthalamic Nucleus (STh) is a lens-shaped subcortical structure located ventrally to the thalamus, that despite being embryologically derived from the diencephalon,... (Review)
Review
The Subthalamic Nucleus (STh) is a lens-shaped subcortical structure located ventrally to the thalamus, that despite being embryologically derived from the diencephalon, is functionally implicated in the basal ganglia circuits. Because of this strict structural and functional relationship with the circuits of the basal ganglia, the STh is a current target for deep brain stimulation, a neurosurgical procedure employed to alleviate symptoms in movement disorders, such as Parkinson's disease and dystonia. However, despite the great relevance of this structure for both basal ganglia physiology and pathology, the neurochemical and molecular anatomy of the STh remains largely unknown. Few studies have specifically addressed the detection of neurotransmitter systems and their receptors within the structure, and even fewer have investigated their topographical distribution. Here, we have reviewed the scientific literature on neurotransmitters relevant in the STh function of rodents, non-human primates and humans including glutamate, GABA, dopamine, serotonin, noradrenaline with particular focus on their subcellular, cellular and topographical distribution. Inter-species differences were highlighted to provide a framework for further research priorities, particularly in humans.
Topics: Animals; Humans; Subthalamic Nucleus; Basal Ganglia; Thalamus; Dopamine; Parkinson Disease
PubMed: 37479801
DOI: 10.1007/s00429-023-02678-z -
Brain : a Journal of Neurology Jun 2021Pain is a frequent and poorly treated symptom of Parkinson's disease, mainly due to scarce knowledge of its basic mechanisms. In Parkinson's disease, deep brain... (Review)
Review
Pain is a frequent and poorly treated symptom of Parkinson's disease, mainly due to scarce knowledge of its basic mechanisms. In Parkinson's disease, deep brain stimulation of the subthalamic nucleus is a successful treatment of motor symptoms, but also might be effective in treating pain. However, it has been unclear which type of pain may benefit and how neurostimulation of the subthalamic nucleus might interfere with pain processing in Parkinson's disease. We hypothesized that the subthalamic nucleus may be an effective access point for modulation of neural systems subserving pain perception and processing in Parkinson's disease. To explore this, we discuss data from human neurophysiological and psychophysical investigations. We review studies demonstrating the clinical efficacy of deep brain stimulation of the subthalamic nucleus for pain relief in Parkinson's disease. Finally, we present some of the key insights from investigations in animal models, healthy humans and Parkinson's disease patients into the aberrant neurobiology of pain processing and consider their implications for the pain-relieving effects of subthalamic nucleus neuromodulation. The evidence from clinical and experimental studies supports the hypothesis that altered central processing is critical for pain generation in Parkinson's disease and that the subthalamic nucleus is a key structure in pain perception and modulation. Future preclinical and clinical research should consider the subthalamic nucleus as an entry point to modulate different types of pain, not only in Parkinson's disease but also in other neurological conditions associated with abnormal pain processing.
Topics: Animals; Deep Brain Stimulation; Humans; Pain; Parkinson Disease; Subthalamic Nucleus
PubMed: 34037696
DOI: 10.1093/brain/awab001 -
Cureus Feb 2018Deep brain stimulation (DBS) is a surgical treatment in which stimulation electrodes are permanently implanted in basal ganglia to treat motor fluctuations and symptoms... (Review)
Review
Deep brain stimulation (DBS) is a surgical treatment in which stimulation electrodes are permanently implanted in basal ganglia to treat motor fluctuations and symptoms of Parkinson's disease (PD). Subthalamic nucleus (STN) and globus pallidus internus (GPi) are the commonly used targets for DBS in PD. Many studies have compared motor and non-motor outcomes of DBS in both targets. However, the selection of PD patients for DBS targets is still poorly studied. Therefore, we performed this narrative review to summarize published studies comparing STN DBS and GPi DBS. GPi DBS is better for patients with problems in speech, mood, or cognition while STN DBS is better from an economic point of view as it allows much reduction in antiparkinson medications and less battery consumption.
PubMed: 29713577
DOI: 10.7759/cureus.2232 -
Neurosurgery Clinics of North America Oct 2017Current knowledge of the functional anatomy of the subthalamic nucleus and globus pallidus, discovered through microelectrode recording and postoperative imaging,... (Review)
Review
Current knowledge of the functional anatomy of the subthalamic nucleus and globus pallidus, discovered through microelectrode recording and postoperative imaging, justifies purely anatomic targeting for deep brain stimulation (DBS). Interventional MRI (iMRI)-DBS is more anatomically accurate than traditional awake procedures and has similar clinical outcomes without increased risk or increased operative times. iMRI lead implantation allows patients to receive DBS therapy who cannot tolerate or do not agree to undergo an awake procedure. This article describes considerations for iMRI-DBS implantation in the subthalamic nucleus and globus pallidus, including patient selection, technique of electrode placement, expected outcomes, and potential complications.
Topics: Deep Brain Stimulation; Electrodes, Implanted; Globus Pallidus; Humans; Magnetic Resonance Imaging, Interventional; Subthalamic Nucleus; Treatment Outcome
PubMed: 28917282
DOI: 10.1016/j.nec.2017.05.007 -
Acta Neurologica Belgica Aug 2021Standard treatment of Parkinson's disease involves the dopaminergic medications. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an important... (Review)
Review
Standard treatment of Parkinson's disease involves the dopaminergic medications. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an important neurosurgical intervention often used as alternative treatment to drug therapy; however, it can be associated with increase of impulsive behaviors. This descriptive review focused on studies investigating the correlation between Deep brain stimulation of the subthalamic nucleus and impulsivity in Parkinson's disease patients, arguing, the action's mechanism and the specific role of the subthalamic nucleus. We searched on PubMed and Web of Science databases and screening references of included studies and review articles for additional citations. From initial 106 studies, only 15 met the search criteria. Parkinson's Disease patients with and without Deep Brain Stimulation were compared with healthy controls, through 16 different tasks that assessed some aspects of impulsivity. Both Deep brain stimulation of the subthalamic nucleus and medication were associated with impulsive behavior and influenced decision-making processes. Moreover, findings demonstrated that: Impulse Control Disorders (ICDs) occurred soon after surgery, while, in pharmacological treatment, they appeared mainly after the initiation of treatment or the increase in dosage, especially with dopamine agonists. The subthalamic nucleus plays a part in the fronto-striato-thalamic-cortical loops mediating motor, cognitive, and emotional functions: this could explain the role of the Deep Brain Stimulation in behavior modulation in Parkinson's Disease patients. Indeed, increase impulsivity has been reported also after deep brain stimulation of the subthalamic nucleus independently by dopaminergic medication status.
Topics: Deep Brain Stimulation; Dopamine; Dopamine Agents; Humans; Impulsive Behavior; Parkinson Disease; Subthalamic Nucleus
PubMed: 33961279
DOI: 10.1007/s13760-021-01684-4 -
Movement Disorders : Official Journal... Mar 2015The subthalamic nucleus (STN), which is currently the most common target for deep brain stimulation (DBS) for Parkinson's disease (PD), has received increased attention... (Review)
Review
The subthalamic nucleus (STN), which is currently the most common target for deep brain stimulation (DBS) for Parkinson's disease (PD), has received increased attention over the past few years for the roles it may play in functions beyond simple motor control. In this article, we highlight several of the theoretical, interventional, and electrophysiological studies that have implicated the STN in response inhibition. Most influential among this evidence has been the reported effect of STN DBS in increasing impulsive responses in the laboratory setting. Yet, how this relates to pathological impulsivity in patients' everyday lives remains uncertain.
Topics: Animals; Biological Clocks; Deep Brain Stimulation; Humans; Models, Neurological; Neural Inhibition; Parkinson Disease; Subthalamic Nucleus
PubMed: 25688872
DOI: 10.1002/mds.26072