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Clinical Neurophysiology : Official... May 2023We studied the relationship between oscillatory activity in the subthalamic nucleus (STN) and speech production in order to better understand the functional role of the...
OBJECTIVE
We studied the relationship between oscillatory activity in the subthalamic nucleus (STN) and speech production in order to better understand the functional role of the STN.
METHODS
We simultaneously recorded subthalamic local field potentials and audio recordings from 5 patients with Parkinson's disease while they performed verbal fluency tasks. We then analyzed the oscillatory signals present in the subthalamic nucleus during these tasks.
RESULTS
We report that normal speech leads to a suppression of subthalamic alpha and beta power. Contrarily, a patient with motor blocks during speech initiation showed a low beta power increase. We also report an increase in error rates in the phonemic non-alternating verbal fluency task during deep brain stimulation (DBS).
CONCLUSIONS
We confirm previous findings that intact speech leads to desynchronization in the beta range in the STN. The speech related narrowband beta power increase in a patient with speech problems suggests that exaggerated synchronization in this frequency band is associated with motor blocks during speech initiation. The increased number of errors in verbal fluency tasks during DBS might be caused by an impairment of the response inhibition network caused by stimulation of the STN.
SIGNIFICANCE
We suggest that the inability to attenuate beta activity during motor processes is associated with motor freezing across motor behaviours such as speech and gait, as previously shown for freezing of gait.
Topics: Humans; Speech; Parkinson Disease; Gait Disorders, Neurologic; Deep Brain Stimulation; Speech Disorders
PubMed: 36893498
DOI: 10.1016/j.clinph.2023.02.166 -
Movement Disorders : Official Journal... Feb 2015Although Parkinson's disease (PD) is primarily considered a disorder of initiation of actions, patients also have deficits in inhibitory control, both in the motor and... (Review)
Review
Although Parkinson's disease (PD) is primarily considered a disorder of initiation of actions, patients also have deficits in inhibitory control, both in the motor and cognitive domains. Impulse control disorders, which can develop in association with dopaminergic medication in a small proportion of patients with PD, are the symptoms most commonly considered as representing inhibitory deficits. However, there is now also a body of evidence suggesting a role for the subthalamic nucleus (STN), which is ordinarily hyperactive in PD, in inhibitory control. Here, we review evidence from animal studies, imaging studies, and investigations recording STN activity intra- or perioperatively in patients with PD having surgery for DBS of the STN (STN-DBS). We also highlight relevant hypotheses about the role of the STN and consider evidence from studies that have examined the effect of STN-DBS in patients with PD on performance of experimental tasks requiring inhibition of prepotent or habitual responses or decision making under conflict, as well as the psychiatric side effects of STN-DBS. Though the results are not always consistent, nevertheless, this body of evidence supports the role of the STN in inhibitory and executive control.
Topics: Animals; Deep Brain Stimulation; Dopamine Agents; Humans; Impulsive Behavior; Inhibition, Psychological; Parkinson Disease; Subthalamic Nucleus
PubMed: 25297382
DOI: 10.1002/mds.26049 -
NeuroImage Apr 2018The substantia nigra (SN), the subthalamic nucleus (STN), and the red nucleus (RN) are midbrain structures of ample interest in many neuroimaging studies, which may... (Review)
Review
The substantia nigra (SN), the subthalamic nucleus (STN), and the red nucleus (RN) are midbrain structures of ample interest in many neuroimaging studies, which may benefit from the availability of automated segmentation methods. The high iron content of these structures awards them high contrast in quantitative susceptibility mapping (QSM) images. We present a novel segmentation method that leverages the information of these images to produce automated segmentations of the SN, STN, and RN. The algorithm builds a map of spatial priors for the structures by non-linearly registering a set of manually-traced training labels to the midbrain. The priors are used to inform a Gaussian mixture model of the image intensities, with smoothness constraints imposed to ensure anatomical plausibility. The method was validated on manual segmentations from a sample of 40 healthy younger and older subjects. Average Dice scores were 0.81 (0.05) for the SN, 0.66 (0.14) for the STN and 0.88 (0.04) for the RN in the left hemisphere, and similar values were obtained for the right hemisphere. In all structures, volumes of manual and automatically obtained segmentations were significantly correlated. The algorithm showed lower accuracy on R and T-weighted Fluid Attenuated Inversion Recovery (FLAIR) images, which are also sensitive to iron content. To illustrate an application of the method, we show that the automated segmentations were comparable to the manual ones regarding detection of age-related differences to putative iron content.
Topics: Adult; Aged; Aging; Female; Humans; Image Processing, Computer-Assisted; Iron; Magnetic Resonance Imaging; Male; Neuroimaging; Red Nucleus; Substantia Nigra; Subthalamic Nucleus
PubMed: 28602813
DOI: 10.1016/j.neuroimage.2017.06.016 -
Acta Neurologica Scandinavica Dec 2022Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a promising palliative option for patients with refractory epilepsy. However, crucial questions remain... (Review)
Review
Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a promising palliative option for patients with refractory epilepsy. However, crucial questions remain unanswered: Which patients are the optimal candidates? How, where, and when to stimulate the STN? And what is the mechanism of STN-DBS action on epilepsy? Thus, we reviewed the clinical evidence on the antiepileptic effects of STN-DBS and its possible mechanisms on drug-resistant epilepsy, its safety, and the factors influencing stimulation outcomes. This information may guide clinical decision-making. In addition, based on the current knowledge on the effect of STN-DBS on epilepsy, we suggest research that needs to be carried out in the future.
Topics: Humans; Subthalamic Nucleus; Deep Brain Stimulation; Parkinson Disease; Drug Resistant Epilepsy
PubMed: 36134756
DOI: 10.1111/ane.13707 -
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 -
PLoS Biology Jun 2023Adapting actions to changing goals and environments is central to intelligent behavior. There is evidence that the basal ganglia play a crucial role in reinforcing or...
Adapting actions to changing goals and environments is central to intelligent behavior. There is evidence that the basal ganglia play a crucial role in reinforcing or adapting actions depending on their outcome. However, the corresponding electrophysiological correlates in the basal ganglia and the extent to which these causally contribute to action adaptation in humans is unclear. Here, we recorded electrophysiological activity and applied bursts of electrical stimulation to the subthalamic nucleus, a core area of the basal ganglia, in 16 patients with Parkinson's disease (PD) on medication using temporarily externalized deep brain stimulation (DBS) electrodes. Patients as well as 16 age- and gender-matched healthy participants attempted to produce forces as close as possible to a target force to collect a maximum number of points. The target force changed over trials without being explicitly shown on the screen so that participants had to infer target force based on the feedback they received after each movement. Patients and healthy participants were able to adapt their force according to the feedback they received (P < 0.001). At the neural level, decreases in subthalamic beta (13 to 30 Hz) activity reflected poorer outcomes and stronger action adaptation in 2 distinct time windows (Pcluster-corrected < 0.05). Stimulation of the subthalamic nucleus reduced beta activity and led to stronger action adaptation if applied within the time windows when subthalamic activity reflected action outcomes and adaptation (Pcluster-corrected < 0.05). The more the stimulation volume was connected to motor cortex, the stronger was this behavioral effect (Pcorrected = 0.037). These results suggest that dynamic modulation of the subthalamic nucleus and interconnected cortical areas facilitates adaptive behavior.
Topics: Humans; Subthalamic Nucleus; Deep Brain Stimulation; Parkinson Disease; Basal Ganglia; Adaptation, Psychological
PubMed: 37262014
DOI: 10.1371/journal.pbio.3002140 -
Clinical Neurophysiology : Official... Dec 2023To assess transcranial sonography (TCS) as stand-alone tool and in combination with microelectrode recordings (MER) as a method for the postoperative localization of...
OBJECTIVE
To assess transcranial sonography (TCS) as stand-alone tool and in combination with microelectrode recordings (MER) as a method for the postoperative localization of deep brain stimulation (DBS) electrodes in the subthalamic nucleus (STN).
METHODS
Individual dorsal and ventral boundaries of STN (n = 12) were determined on intraoperative MER. Postoperatively, a standardized TCS protocol was applied to measure medio-lateral, anterior-posterior and rostro-caudal electrode position using visualized reference structures (midline, substantia nigra). TCS and combined TCS-MER data were validated using fusion-imaging and clinical outcome data.
RESULTS
Test-retest reliability of standard TCS measures of electrode position was excellent. Computed tomography and TCS measures of distance between distal electrode contact and midline agreed well (Pearson correlation; r = 0.86; p < 0.001). Comparing our "gold standard" of rostro-caudal electrode localization relative to STN boundaries, i.e. combining MRI-based stereotaxy and MER data, with the combination of TCS and MER data, the measures differed by 0.32 ± 0.87 (range, -1.35 to 1.25) mm. Combined TCS-MER data identified the clinically preferred electrode contacts for STN-DBS with high accuracy (Coheńs kappa, 0.86).
CONCLUSIONS
Combined TCS-MER data allow for exact localization of STN-DBS electrodes.
SIGNIFICANCE
Our method provides a new option for monitoring of STN-DBS electrode location and guidance of DBS programming in Parkinson's disease.
Topics: Humans; Parkinson Disease; Microelectrodes; Reproducibility of Results; Deep Brain Stimulation; Subthalamic Nucleus; Magnetic Resonance Imaging; Electrodes, Implanted
PubMed: 37972531
DOI: 10.1016/j.clinph.2023.11.001 -
Brain : a Journal of Neurology Jun 2024Control of actions allows adaptive, goal-directed behaviour. The basal ganglia, including the subthalamic nucleus, are thought to play a central role in dynamically...
Control of actions allows adaptive, goal-directed behaviour. The basal ganglia, including the subthalamic nucleus, are thought to play a central role in dynamically controlling actions through recurrent negative feedback loops with the cerebral cortex. Here, we summarize recent translational studies that used deep brain stimulation to record neural activity from and apply electrical stimulation to the subthalamic nucleus in people with Parkinson's disease. These studies have elucidated spatial, spectral and temporal features of the neural mechanisms underlying the controlled delay of actions in cortico-subthalamic networks and demonstrated their causal effects on behaviour in distinct processing windows. While these mechanisms have been conceptualized as control signals for suppressing impulsive response tendencies in conflict tasks and as decision threshold adjustments in value-based and perceptual decisions, we propose a common framework linking decision-making, cognition and movement. Within this framework subthalamic deep brain stimulation can lead to suboptimal choices by reducing the time that patients take for deliberation before committing to an action. However, clinical studies have consistently shown that the occurrence of impulse control disorders is reduced, not increased, after subthalamic deep brain stimulation surgery. This apparent contradiction can be reconciled when recognizing the multifaceted nature of impulsivity, its underlying mechanisms and modulation by treatment. While subthalamic deep brain stimulation renders patients susceptible to making decisions without proper forethought, this can be disentangled from effects related to dopamine comprising sensitivity to benefits vs. costs, reward delay aversion and learning from outcomes. Alterations in these dopamine-mediated mechanisms are thought to underlie the development of impulse control disorders, and can be relatively spared with reduced dopaminergic medication after subthalamic deep brain stimulation. Together, results from studies using deep brain stimulation as an experimental tool have improved our understanding of action control in the human brain and have important implications for treatment of patients with Neurological disorders.
PubMed: 38869168
DOI: 10.1093/brain/awae184 -
Brain Communications 2023Huntington's and Parkinson's disease are two movement disorders representing mainly opposite states of the basal ganglia inhibitory function. Despite being an integral...
Huntington's and Parkinson's disease are two movement disorders representing mainly opposite states of the basal ganglia inhibitory function. Despite being an integral part of the cortico-subcortico-cortical circuitry, the subthalamic nucleus function has been studied at the level of detail required to isolate its signal only through invasive studies in Huntington's and Parkinson's disease. Here, we tested whether the subthalamic nucleus exhibited opposite functional signatures in early Huntington's and Parkinson's disease. We included both movement disorders in the same whole-brain imaging study, and leveraged ultra-high-field 7T MRI to achieve the very fine resolution needed to investigate the smallest of the basal ganglia nuclei. Eleven of the 12 Huntington's disease carriers were recruited at a premanifest stage, while 16 of the 18 Parkinson's disease patients only exhibited unilateral motor symptoms (15 were at Stage I of Hoehn and Yahr off medication). Our group comparison interaction analyses, including 24 healthy controls, revealed a differential effect of Huntington's and Parkinson's disease on the functional connectivity at rest of the subthalamic nucleus within the sensorimotor network, i.e. an opposite effect compared with their respective age-matched healthy control groups. This differential impact in the subthalamic nucleus included an area precisely corresponding to the deep brain stimulation 'sweet spot'-the area with maximum overall efficacy-in Parkinson's disease. Importantly, the severity of deviation away from controls' resting-state values in the subthalamic nucleus was associated with the severity of motor and cognitive symptoms in both diseases, despite functional connectivity going in directions in each disorder. We also observed an altered, opposite impact of Huntington's and Parkinson's disease on functional connectivity within the sensorimotor cortex, once again with relevant associations with clinical symptoms. The high resolution offered by the 7T scanner has thus made it possible to explore the complex interplay between the disease effects and their contribution on the subthalamic nucleus, and sensorimotor cortex. Taken altogether, these findings reveal for the first time non-invasively in humans a differential, clinically meaningful impact of the pathophysiological process of these two movement disorders on the overall sensorimotor functional connection of the subthalamic nucleus and sensorimotor cortex.
PubMed: 38075949
DOI: 10.1093/braincomms/fcad282 -
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