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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 -
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 -
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 -
Movement Disorders : Official Journal... Jun 2023
Topics: Humans; Parkinson Disease; Subthalamic Nucleus; Deep Brain Stimulation
PubMed: 37475610
DOI: 10.1002/mds.29409 -
Neuron May 2020The ability to dynamically change motor outputs, such as stopping an initiated response, is an important aspect of human behavior. A hyperdirect pathway between the...
The ability to dynamically change motor outputs, such as stopping an initiated response, is an important aspect of human behavior. A hyperdirect pathway between the inferior frontal gyrus and subthalamic nucleus is hypothesized to mediate movement inhibition, but there is limited evidence for this in humans. We recorded high spatial and temporal resolution field potentials from both the inferior frontal gyrus and subthalamic nucleus in 21 subjects. Cortical potentials evoked by subthalamic stimulation revealed short latency events indicative of monosynaptic connectivity between the inferior frontal gyrus and ventral subthalamic nucleus. During a stop signal task, stopping-related potentials in the cortex preceded stopping-related activity in the subthalamic nucleus, and synchronization between these task-evoked potentials predicted the stop signal reaction time. Thus, we show that a prefrontal-subthalamic hyperdirect pathway is present in humans and mediates rapid stopping. These findings may inform therapies to treat disorders featuring perturbed movement inhibition.
Topics: Aged; Electrocorticography; Female; Humans; Inhibition, Psychological; Male; Middle Aged; Movement; Neural Pathways; Parkinson Disease; Prefrontal Cortex; Subthalamic Nucleus
PubMed: 32155442
DOI: 10.1016/j.neuron.2020.02.012 -
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 Stimulation 2020Deep brain stimulation (DBS) of the subthalamic region is an established treatment for the motor symptoms of Parkinson's disease. Several types of neural elements reside...
BACKGROUND
Deep brain stimulation (DBS) of the subthalamic region is an established treatment for the motor symptoms of Parkinson's disease. Several types of neural elements reside in the subthalamic region, including subthalamic nucleus (STN) neurons, fibers of passage, and terminating afferents. Recent studies suggest that direct activation of a specific population of subthalamic afferents, known as the hyperdirect pathway, may be responsible for some of the therapeutic effects of subthalamic DBS.
OBJECTIVE
The goal of this study was to quantify how axon termination affects neural excitability from DBS. We evaluated how adjusting different stimulation parameters influenced the relative excitability of terminating axons (TAs) compared to fibers of passage (FOPs).
METHODS
We used finite element electric field models of DBS, coupled to multi-compartment cable models of axons, to calculate activation thresholds for populations of TAs and FOPs. These generalized models were used to evaluate the response to anodic vs. cathodic stimulation, with short vs. long stimulus pulses.
RESULTS
Terminating axons generally exhibited lower thresholds than fibers of passage across all tested parameters. Short pulse widths accentuated the relative excitability of TAs over FOPs.
CONCLUSION(S)
Our computational results demonstrate a hyperexcitability of terminating axons to DBS that is robust to variation in the stimulation parameters, as well as the axon model parameters.
Topics: Axons; Deep Brain Stimulation; Electrodes, Implanted; Humans; Neurons; Parkinson Disease; Subthalamic Nucleus
PubMed: 32919091
DOI: 10.1016/j.brs.2020.09.001 -
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 -
Clinical Neurophysiology : Official... May 2018This study aims to use the activities recorded directly from the deep brain stimulation (DBS) electrode to address the focality and distinct nature of the local field...
OBJECTIVE
This study aims to use the activities recorded directly from the deep brain stimulation (DBS) electrode to address the focality and distinct nature of the local field potential (LFP) activities of different frequency.
METHODS
Pre-operative and intra-operative magnetic resonance imaging (MRI) were acquired from patients with Parkinson's disease (PD) who underwent DBS in the subthalamic nucleus and intra-operative LFP recording at rest and during cued movements. Images were reconstructed and 3-D visualized using Lead-DBS® toolbox to determine the coordinates of contact. The resting spectral power and movement-related power modulation of LFP oscillations were estimated.
RESULTS
Both subthalamic LFP activity recorded at rest and its modulation by movement had focal maxima in the alpha, beta and gamma bands. The spatial distribution of alpha band activity and its modulation was significantly different to that in the beta band. Moreover, there were significant differences in the scale and timing of movement related modulation across the frequency bands.
CONCLUSION
Subthalamic LFP activities within specific frequency bands can be distinguished by spatial topography and pattern of movement related modulation.
SIGNIFICANCE
Assessment of the frequency, focality and pattern of movement related modulation of subthalamic LFPs reveals a heterogeneity of neural population activity in this region. This could potentially be leveraged to finesse intra-operative targeting and post-operative contact selection.
Topics: Action Potentials; Aged; Biosensing Techniques; Deep Brain Stimulation; Female; Humans; Male; Middle Aged; Movement; Parkinson Disease; Subthalamic Nucleus
PubMed: 29567582
DOI: 10.1016/j.clinph.2018.01.075 -
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