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Scientific Reports Aug 2017We aimed to explore the effects of bilateral subthalamic nucleus stimulation and levodopa on cardiovascular autonomic function in Parkinson's disease. Twenty-six...
We aimed to explore the effects of bilateral subthalamic nucleus stimulation and levodopa on cardiovascular autonomic function in Parkinson's disease. Twenty-six Parkinson's disease patients with bilateral subthalamic nucleus stimulation in a stable state were tested under stimulation off and dopaminergic medication off (OFF-OFF), stimulation on and dopaminergic medication off (ON-OFF), and stimulation on and medication (levodopa) on (ON-ON) conditions by recording continuously blood pressure, ECG, and respiration at rest, during metronomic deep breathing, and head-up tilt test. Thirteen patients were diagnosed as orthostatic hypotension by head-up tilt test. Baroreflex sensitivity and spectral analyses were performed by trigonometric regressive spectral analysis. Subthalamic nucleus stimulation and levodopa had multiple influences. (1) Systolic blood pressure during tilt-up was reduced by subthalamic nucleus stimulation, and then further by levodopa. (2) Subthalamic nucleus stimulation and levodopa had different effects on sympathetic and parasympathetic regulations in Parkinson's disease. (3) Levodopa decreased baroreflex sensitivity and RR interval only in the orthostatic hypotension group, and had opposite effects on the non-orthostatic hypotension group. These findings indicate that subthalamic nucleus stimulation and levodopa have different effects on cardiovascular autonomic function in Parkinson's disease, which are modulated by the presence of orthostatic hypotension as well.
Topics: Aged; Antiparkinson Agents; Blood Pressure; Cardiovascular Physiological Phenomena; Deep Brain Stimulation; Electrocardiography; Female; Humans; Levodopa; Male; Middle Aged; Parkinson Disease; Respiration; Subthalamic Nucleus
PubMed: 28765629
DOI: 10.1038/s41598-017-07429-9 -
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 -
Brain Communications 2022Selecting the ideal contact to apply subthalamic nucleus deep brain stimulation in Parkinson's disease can be an arduous process, with outcomes highly dependent on...
Selecting the ideal contact to apply subthalamic nucleus deep brain stimulation in Parkinson's disease can be an arduous process, with outcomes highly dependent on clinician expertise. This study aims to assess whether neuronal signals recorded intraoperatively in awake patients, and the anatomical location of contacts, can assist programming. In a cohort of 14 patients with Parkinson's disease, implanted with subthalamic nucleus deep brain stimulation, the four contacts on each lead in the 28 hemispheres were ranked according to proximity to a nominated ideal anatomical location and power of the following neuronal signals: evoked resonant neural activity, beta oscillations and high-frequency oscillations. We assessed how these rankings predicted, on each lead: (i) the motor benefit from deep brain stimulation applied through each contact and (ii) the 'ideal' contact to apply deep brain stimulation. The ranking of contacts according to each factor predicted motor benefit from subthalamic nucleus deep brain stimulation, as follows: evoked resonant neural activity; = 0.50, Akaike information criterion 1039.9, beta; = 0.50, Akaike information criterion 1041.6, high-frequency oscillations; = 0.44, Akaike information criterion 1057.2 and anatomy; = 0.49, Akaike information criterion 1048.0. Combining evoked resonant neural activity, beta and high-frequency oscillations ranking data yielded the strongest predictive model ( = 0.61, Akaike information criterion 1021.5). The 'ideal' contact (yielding maximal benefit) was ranked first according to each factor in the following proportion of hemispheres; evoked resonant neural activity 18/28, beta 17/28, anatomy 16/28, high-frequency oscillations 7/28. Across hemispheres, the maximal available deep brain stimulation benefit did not differ from that yielded by contacts chosen by clinicians for chronic therapy or contacts ranked first according to evoked resonant neural activity. Evoked resonant neural activity, beta oscillations and anatomy similarly predicted how motor benefit from subthalamic nucleus deep brain stimulation varied across contacts on each lead. This could assist programming by providing a probability ranking of contacts akin to a 'monopolar survey'. However, these factors identified the 'ideal' contact in only a proportion of hemispheres. More advanced signal processing and anatomical techniques may be needed for the full automation of contact selection.
PubMed: 35169708
DOI: 10.1093/braincomms/fcac003 -
Reviews in the Neurosciences 2013Because the complex functions of the basal ganglia have been increasingly studied over the past several decades, the understanding of the role of the subthalamic nucleus... (Review)
Review
Because the complex functions of the basal ganglia have been increasingly studied over the past several decades, the understanding of the role of the subthalamic nucleus (STN) in motor and cognitive functions has evolved. The traditional role in motor function ascribed to the STN, based on its involvement in the cortico-striato-thalamo-cortical motor loops, the pathologic STN activity seen in Parkinson's disease, and the benefits in motor symptoms following STN lesions and deep brain stimulation, has been revised to include wider cognitive functions. The increased attention focused on such nonmotor functions housed within the STN partially arose from the observed cognitive and affective side effects seen with STN deep brain stimulation. The multiple modalities of research have corroborated these findings and have provided converging evidence that the STN is critically involved in cognitive processes. In particular, numerous experiments have demonstrated the involvement of the STN in high-conflict decisions. The different STN functions appear to be related to activity in anatomically distinct subregions, with the ventral STN contributing to high-conflict decision-making through its role in the hyperdirect pathway involving the prefrontal cortex.
Topics: Animals; Cognition; Humans; Subthalamic Nucleus
PubMed: 23327862
DOI: 10.1515/revneuro-2012-0075 -
Indian Journal of Ophthalmology May 2014This review focuses on saccadic eye movement research in Parkinson's disease (PD) patients. Results from various studies related to Parkinson disease and saccades have... (Review)
Review
This review focuses on saccadic eye movement research in Parkinson's disease (PD) patients. Results from various studies related to Parkinson disease and saccades have been discussed in terms of various saccadic parameters like latency, amplitude, velocity and gain. Neural circuitry of saccadic eye movements and cognitive processes and it's relation with altered saccadic performance in Parkinson disease has been discussed here. This article also covers various research paradigms commonly used to study saccades. Effects of medication on saccadic parameters in PD patients have also been discussed along with the effects of deep brain stimulation of subthalamic nucleus on saccadic performance in PD patients. Literature review was done using online Pubmed search engine and National Medical Library.
Topics: Humans; Parkinson Disease; Saccades; Subthalamic Nucleus
PubMed: 24881597
DOI: 10.4103/0301-4738.133482 -
Journal of Neurology, Neurosurgery, and... Jun 2002
Topics: Aged; Depression; Electric Stimulation Therapy; Family Health; Humans; Motor Skills Disorders; Parkinson Disease; Social Behavior; Subthalamic Nucleus; Suicide
PubMed: 12023406
DOI: 10.1136/jnnp.72.6.689 -
Cerebral Cortex (New York, N.Y. : 1991) Apr 2020The subthalamic nucleus (STN) is proposed to participate in pausing, or alternately, in dynamic scaling of behavioral responses, roles that have conflicting implications...
The subthalamic nucleus (STN) is proposed to participate in pausing, or alternately, in dynamic scaling of behavioral responses, roles that have conflicting implications for understanding STN function in the context of deep brain stimulation (DBS) therapy. To examine the nature of event-related STN activity and subthalamic-cortical dynamics, we performed primary motor and somatosensory electrocorticography while subjects (n = 10) performed a grip force task during DBS implantation surgery. Phase-locking analyses demonstrated periods of STN-cortical coherence that bracketed force transduction, in both beta and gamma ranges. Event-related causality measures demonstrated that both STN beta and gamma activity predicted motor cortical beta and gamma activity not only during force generation but also prior to movement onset. These findings are consistent with the idea that the STN participates in motor planning, in addition to the modulation of ongoing movement. We also demonstrated bidirectional information flow between the STN and somatosensory cortex in both beta and gamma range frequencies, suggesting robust STN participation in somatosensory integration. In fact, interactions in beta activity between the STN and somatosensory cortex, and not between STN and motor cortex, predicted PD symptom severity. Thus, the STN contributes to multiple aspects of sensorimotor behavior dynamically across time.
Topics: Adult; Aged; Deep Brain Stimulation; Electrocorticography; Electrodes, Implanted; Female; Hand Strength; Humans; Male; Middle Aged; Motor Cortex; Psychomotor Performance; Somatosensory Cortex; Subthalamic Nucleus
PubMed: 31989165
DOI: 10.1093/cercor/bhz264 -
Brain Structure & Function Nov 2015Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is used to relieve motor symptoms of Parkinson's disease. A tripartite system of STN subdivisions serving... (Review)
Review
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is used to relieve motor symptoms of Parkinson's disease. A tripartite system of STN subdivisions serving motoric, associative, and limbic functions was proposed, mainly based on tracing studies, which are limited by low numbers of observations. The evidence is compelling and raises the question as to what extent these functional zones are anatomically segregated. The majority of studies indicate that there is anatomical overlap between STN functional zones. Using ultrahigh-resolution magnetic resonance imaging techniques it is now possible to visualize the STN with high spatial resolution, and it is feasible that in the near future stereotactic guided placement of electrical stimulators aided by high-resolution imaging will allow for more specific stimulation of the STN. The neuroanatomical and functional makeup of these subdivisions and their level of overlap would benefit from clarification before serving as surgical targets. We discuss histological and imaging studies, as well as clinical observations and electrophysiological recordings in DBS patients. These studies provide evidence for a topographical organization within the STN, although it remains unclear to what extent functionally and anatomically distinct subdivisions overlap.
Topics: Animals; Basal Ganglia; Brain Mapping; Deep Brain Stimulation; Humans; Magnetic Resonance Imaging; Primates; Structure-Activity Relationship; Subthalamic Nucleus
PubMed: 25921975
DOI: 10.1007/s00429-015-1047-2 -
Neuron Mar 2021The subthalamic nucleus (STN) supports action selection by inhibiting all motor programs except the desired one. Recent evidence suggests that STN can also cancel an...
The subthalamic nucleus (STN) supports action selection by inhibiting all motor programs except the desired one. Recent evidence suggests that STN can also cancel an already selected action when goals change, a key aspect of cognitive control. However, there is little neurophysiological evidence for dissociation between selecting and cancelling actions in the human STN. We recorded single neurons in the STN of humans performing a stop-signal task. Movement-related neurons suppressed their activity during successful stopping, whereas stop-signal neurons activated at low-latencies near the stop-signal reaction time. In contrast, STN and motor-cortical beta-bursting occurred only later in the stopping process. Task-related neuronal properties varied by recording location from dorsolateral movement to ventromedial stop-signal tuning. Therefore, action selection and cancellation coexist in STN but are anatomically segregated. These results show that human ventromedial STN neurons carry fast stop-related signals suitable for implementing cognitive control.
Topics: Aged; Female; Humans; Inhibition, Psychological; Male; Middle Aged; Movement; Neurons; Psychomotor Performance; Reaction Time; Subthalamic Nucleus
PubMed: 33482087
DOI: 10.1016/j.neuron.2020.12.025 -
The Neuroscientist : a Review Journal... Feb 2019How do we decide what we do? This is the essence of action control, the process of selecting the most appropriate response among multiple possible choices. Suboptimal... (Review)
Review
How do we decide what we do? This is the essence of action control, the process of selecting the most appropriate response among multiple possible choices. Suboptimal action control can involve a failure to initiate or adapt actions, or conversely it can involve making actions impulsively. There has been an increasing focus on the specific role of the subthalamic nucleus (STN) in action control. This has been fueled by the clinical relevance of this basal ganglia nucleus as a target for deep brain stimulation (DBS), primarily in Parkinson's disease but also in obsessive-compulsive disorder. The context of DBS has opened windows to study STN function in ways that link neuroscientific and clinical fields closely together, contributing to an exceptionally high level of two-way translation. In this review, we first outline the role of the STN in both motor and nonmotor action control, and then discuss how these functions might be implemented by neuronal activity in the STN. Gaining a better understanding of these topics will not only provide important insights into the neurophysiology of action control but also the pathophysiological mechanisms relevant for several brain disorders and their therapies.
Topics: Animals; Brain Waves; Conflict, Psychological; Decision Making; Deep Brain Stimulation; Humans; Movement; Neural Pathways; Subthalamic Nucleus; Voltage-Dependent Anion Channels
PubMed: 29557710
DOI: 10.1177/1073858418763594