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Neuroscience and Biobehavioral Reviews Jan 2022Understanding the pathophysiological mechanism of Parkinson's disease (PD) in the subthalamic nucleus (STN) has become a critical issue since deep brain stimulation... (Review)
Review
Understanding the pathophysiological mechanism of Parkinson's disease (PD) in the subthalamic nucleus (STN) has become a critical issue since deep brain stimulation (DBS) in this region has been proven as an effective treatment for this disease. The STN possesses a special ability to switch from the spike to the burst firing mode in response to dopamine deficiency in parkinsonism, and this STN burst is considered an electrophysiological signature of the cortico-basal ganglia circuit in the brains of PD patients. This review focuses on the role of STN burst firing in the pathophysiology of PD and during DBS. Here, we review existing literature on how STN bursts originate and the specific factors affecting their formation; how STN burst firing causes motor symptoms in PD and how interventions can rescue these symptoms. Finally, the similarities and differences between the two electrophysiological hallmarks of PD, STN burst firing and beta-oscillation, are discussed. STN burst firing should be considered as a pathophysiological target in PD during treatment with DBS.
Topics: Basal Ganglia; Deep Brain Stimulation; Humans; Parkinson Disease; Parkinsonian Disorders; Subthalamic Nucleus
PubMed: 34856222
DOI: 10.1016/j.neubiorev.2021.11.044 -
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 -
Brain : a Journal of Neurology Feb 2021The subthalamic nucleus is part of a global stopping network that also includes the presupplementary motor area and inferior frontal gyrus of the right hemisphere. In...
The subthalamic nucleus is part of a global stopping network that also includes the presupplementary motor area and inferior frontal gyrus of the right hemisphere. In Parkinson's disease, subthalamic deep brain stimulation improves movement initiation and velocity, but its effect on stopping of ongoing movement is unknown. Here, we examine the relation between movement stopping and connectivity of stimulation volumes to the stopping network. Stop and go times were collected in 17 patients with Parkinson's disease on and off subthalamic stimulation during visually cued initiation and termination of continuous, rotational movements. Deep brain stimulation contacts were localized; the stimulation volume computed and connectivity profiles estimated using an openly available, normative structural connectome. Subthalamic stimulation significantly increased stop times, which correlated with the connectivity of the stimulation volume to presupplementary motor area and inferior frontal gyrus of the right hemisphere. The robustness of this finding was validated using three separate analysis streams: voxel-wise whole-brain connectivity, region of interest connectivity and a tract-centred method. Our study sheds light on the role of the fronto-subthalamic inhibitory triangle in stopping of ongoing movements and may inspire circuit based adaptive stimulation strategies for control of stopping impairment, possibly reflected in stimulation-induced dyskinesia.
Topics: Aged; Brain; Connectome; Deep Brain Stimulation; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Movement; Neural Pathways; Parkinson Disease; Subthalamic Nucleus
PubMed: 33253351
DOI: 10.1093/brain/awaa341 -
Parkinsonism & Related Disorders Mar 2022Deep brain stimulation of the subthalamic nucleus is effective to alleviate motor symptoms in advanced Parkinson's disease. Using a novel conditioning paradigm, it has...
BACKGROUND
Deep brain stimulation of the subthalamic nucleus is effective to alleviate motor symptoms in advanced Parkinson's disease. Using a novel conditioning paradigm, it has been shown that deep brain stimulation pulses from electrodes in the subthalamic nucleus modulate corticospinal excitability as determined with transcranial magnetic stimulation applied to the motor cortex. The mechanism of action is unclear.
OBJECTIVE
To investigate the effects of subthalamic nucleus and dorsal premotor cortex conditioning on corticospinal excitability as a function of interstimulus intervals between target areas and deep brain stimulation frequencies.
METHODS
In 19 patients with Parkinson's disease with subthalamic nucleus deep brain stimulation, the premotor-motor interaction was investigated in four different deep brain stimulation conditions (off, clinically used settings, 3 Hz, 20 Hz). Transcranial magnetic pulses were applied to the premotor and motor cortex and paired at certain intervals with deep brain stimulation pulses. The volume of tissue activated by deep brain stimulation was correlated with neurophysiological findings.
RESULTS
There was distinct motor cortex inhibition by premotor cortex conditioning at an interstimulus interval of 1 ms before the motor cortex stimulation. Subthalamic nucleus conditioning with deep brain stimulation frequencies of 3 and 20 Hz at an interstimulus interval of 10 ms between subthalamic nucleus and primary motor cortex reduced premotor-motor inhibition. The volume of tissue activated by deep brain stimulation correlated positively with this effect. Corticospinal excitability was not affected by subthalamic nucleus conditioning as used here.
CONCLUSIONS
Premotor-motor inhibition is modulated by subthalamic nucleus conditioning, presumably through the monosynaptic hyperdirect pathway.
Topics: Deep Brain Stimulation; Humans; Motor Cortex; Parkinson Disease; Subthalamic Nucleus; Transcranial Magnetic Stimulation
PubMed: 35093853
DOI: 10.1016/j.parkreldis.2022.01.014 -
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 -
The Lancet. Neurology Oct 2013Electrical stimulation of the subthalamic nucleus is an established treatment for patients with advanced Parkinson's disease with pharmacologically unresponsive... (Meta-Analysis)
Meta-Analysis Review
Electrical stimulation of the subthalamic nucleus is an established treatment for patients with advanced Parkinson's disease with pharmacologically unresponsive fluctuations. Compared with pharmacological treatment, subthalamic neurostimulation significantly improves motor symptoms, particularly during the phases of poor response to drug treatment, and reduces the severity of dyskinesias. Importantly, it also significantly improves quality of life and other integral measures of disease severity. The treatment response can last for more than 10 years, although there is no evidence that levodopa-resistant symptoms are delayed by subthalamic neurostimulation. At present, the mean disease duration for patients at the time of implantation is 12 years. In a recent study (EARLYSTIM) in patients with a disease duration of 7·5 years and fluctuations for 1·5 years, similar improvements in clinical outcomes were reported. These findings suggest that neurostimulation of the subthalamic nucleus could be used earlier in the disease course for carefully selected patients if the benefits of the treatment are weighed against the surgical risks and the lifelong need for specialised care by an experienced team. As mobility is consistently improved during the times with poor mobility by reducing fluctuations and delaying levodopa-sensitive complications, we propose that this treatment changes the disease course.
Topics: Deep Brain Stimulation; Disease Progression; Humans; Parkinson Disease; Risk Factors; Subthalamic Nucleus
PubMed: 24050735
DOI: 10.1016/S1474-4422(13)70151-0 -
Neuroscience and Biobehavioral Reviews Mar 2013Affective neuroscience is concerned with identifying the neural bases of emotion. For historical and methodological reasons, models describing the brain architecture... (Review)
Review
Affective neuroscience is concerned with identifying the neural bases of emotion. For historical and methodological reasons, models describing the brain architecture that supports emotional processes in humans have tended to neglect the basal ganglia, focusing instead on cortical and amygdalar mechanisms. Now, however, deep brain stimulation (DBS) of the subthalamic nucleus (STN), a neurosurgical treatment for Parkinson's disease and obsessive-compulsive disorder, is helping researchers explore the possible functional role of this particular basal ganglion in emotional processes. After reviewing studies that have used DBS in this way, we propose a model in which the STN plays a crucial role in producing temporally organized neural co-activation patterns at the cortical and subcortical levels that are essential for generating emotions and related feelings.
Topics: Animals; Basal Ganglia; Cortical Synchronization; Emotions; Humans; Neural Pathways; Parkinson Disease; Subthalamic Nucleus
PubMed: 23318227
DOI: 10.1016/j.neubiorev.2013.01.001 -
Subthalamic beta oscillations correlate with dopaminergic degeneration in experimental parkinsonism.Experimental Neurology Jan 2021Excessive beta activity has been shown in local field potential recordings from the cortico-basal ganglia loop of Parkinson's disease patients and in its various animal...
Excessive beta activity has been shown in local field potential recordings from the cortico-basal ganglia loop of Parkinson's disease patients and in its various animal models. Recent evidence suggests that enhanced beta oscillations may play a central role in the pathophysiology of the disorder and that beta activity may be directly linked to the motor impairment. However, the temporal evolution of exaggerated beta oscillations during the ongoing dopaminergic neurodegeneration and its relation to the motor impairment and histological changes are still unknown. We investigated motor behavioral, in-vivo electrophysiological (subthalamic nucleus, motor cortex) and histological changes (striatum, substantia nigra compacta) 2, 5, 10 and 20-30 days after a 6-hydroxydopamine injection into the medial forebrain bundle in Wistar rats. We found strong correlations between subthalamic beta power and motor impairment. No correlation was found for beta power in the primary motor cortex. Only subthalamic but not cortical beta power was strongly correlated with the histological markers of the dopaminergic neurodegeneration. Significantly increased subthalamic beta oscillations could be detected before this increase was found in primary motor cortex. At the latest observation time point, a significantly higher percentage of long beta bursts was found. Our study is the first to show a strong relation between subthalamic beta power and the dopaminergic neurodegeneration. Thus, we provide additional evidence for an important pathophysiological role of subthalamic beta oscillations and prolonged beta bursts in Parkinson's disease.
Topics: Animals; Beta Rhythm; Deep Brain Stimulation; Dopaminergic Neurons; Electroencephalography; Electrophysiological Phenomena; Hydroxydopamines; Male; Motor Cortex; Movement Disorders; Neostriatum; Nerve Degeneration; Parkinsonian Disorders; Rats; Subthalamic Nucleus; Treatment Outcome
PubMed: 33148526
DOI: 10.1016/j.expneurol.2020.113513 -
Nature Communications Apr 2022The subthalamic nucleus projects to the external and internal pallidum, the modulatory and output nuclei of the basal ganglia, respectively, and plays an indispensable...
The subthalamic nucleus projects to the external and internal pallidum, the modulatory and output nuclei of the basal ganglia, respectively, and plays an indispensable role in controlling voluntary movements. However, the precise mechanism by which the subthalamic nucleus controls pallidal activity and movements remains elusive. Here, we utilize chemogenetics to reversibly reduce neural activity of the motor subregion of the subthalamic nucleus in three macaque monkeys (Macaca fuscata, both sexes) during a reaching task. Systemic administration of chemogenetic ligands prolongs movement time and increases spike train variability in the pallidum, but only slightly affects firing rate modulations. Across-trial analyses reveal that the irregular discharges in the pallidum coincides with prolonged movement time. Reduction of subthalamic activity also induces excessive abnormal movements in the contralateral forelimb, which are preceded by subthalamic and pallidal phasic activity changes. Our results suggest that the subthalamic nucleus stabilizes pallidal spike trains and achieves stable movements.
Topics: Animals; Basal Ganglia; Globus Pallidus; Haplorhini; Movement; Subthalamic Nucleus
PubMed: 35468893
DOI: 10.1038/s41467-022-29750-2