The promotion-like effect of the M1-STN hyperdirect pathway induced by ccPAS enhanced balance performances: From the perspective of brain connectivity.

AIMS: The present study aimed to explore the effect of cortico-cortical paired-associative stimulation (ccPAS) in modulating hyperdirect pathway and its influence on balance performance. METHODS: Forty healthy participants were randomly allocated to the active ccPAS group (n = 20) or the sham ccPAS group (n = 20). The primary motor cortex and subthalamic nucleus were stimulated sequentially with ccPAS. Unlike the active ccPAS group, one wing of coil was tilted to form a 90° angle with scalp of stimulation locations for the sham ccPAS group. Magnetic resonance imaging, functional reach test (FRT), timed up and go (TUG) test, and limit of stability (LOS) test were performed, and correlation between them was also analyzed. RESULTS: Three participants in the sham ccPAS group were excluded because of poor quality of NIfTI images. The active group had strengthened hyperdirect pathway, increased functional connectivity (FC) between orbital part of frontal cortex and bilateral precuneus, and decreased FC among basal ganglia (all p < 0.05). Regional network properties of triangular and orbital parts of IFG, middle cingulate cortex, and hippocampus increased. The active group performed better in FRT and LOS (all p < 0.05). FRT positively correlated with FC of the hyperdirect pathway (r = 0.439, p = 0.007) and FCs between orbital part of frontal cortex and bilateral precuneus (all p < 0.05). CONCLUSION: The ccPAS enhanced balance performance by promotion-like plasticity mechanisms through the hyperdirect pathway.

Neural signatures of indirect pathway activity during subthalamic stimulation in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) produces an electrophysiological signature called evoked resonant neural activity (ERNA); a high-frequency oscillation that has been linked to treatment efficacy. However, the single-neuron and synaptic bases of ERNA are unsubstantiated. This study proposes that ERNA is a subcortical neuronal circuit signature of DBS-mediated engagement of the basal ganglia indirect pathway network. In people with Parkinson's disease, we: (i) showed that each peak of the ERNA waveform is associated with temporally-locked neuronal inhibition in the STN; (ii) characterized the temporal dynamics of ERNA; (iii) identified a putative mesocircuit architecture, embedded with empirically-derived synaptic dynamics, that is necessary for the emergence of ERNA in silico; (iv) localized ERNA to the dorsal STN in electrophysiological and normative anatomical space; (v) used patient-wise hotspot locations to assess spatial relevance of ERNA with respect to DBS outcome; and (vi) characterized the local fiber activation profile associated with the derived group-level ERNA hotspot.

Subthalamic stimulation modulates context-dependent effects of beta bursts during fine motor control.

Increasing evidence suggests a considerable role of pre-movement beta bursts for motor control and its impairment in Parkinson's disease. However, whether beta bursts occur during precise and prolonged movements and if they affect fine motor control remains unclear. To investigate the role of within-movement beta bursts for fine motor control, we here combine invasive electrophysiological recordings and clinical deep brain stimulation in the subthalamic nucleus in 19 patients with Parkinson's disease performing a context-varying task that comprised template-guided and free spiral drawing. We determined beta bursts in narrow frequency bands around patient-specific peaks and assessed burst amplitude, duration, and their immediate impact on drawing speed. We reveal that beta bursts occur during the execution of drawing movements with reduced duration and amplitude in comparison to rest. Exclusively when drawing freely, they parallel reductions in acceleration. Deep brain stimulation increases the acceleration around beta bursts in addition to a general increase in drawing velocity and improvements of clinical function. These results provide evidence for a diverse and task-specific role of subthalamic beta bursts for fine motor control in Parkinson's disease; suggesting that pathological beta bursts act in a context dependent manner, which can be targeted by clinical deep brain stimulation.

Gait-related beta-gamma phase amplitude coupling in the subthalamic nucleus of parkinsonian patients.

Analysis of coupling between the phases and amplitudes of neural oscillations has gained increasing attention as an important mechanism for large-scale brain network dynamics. In Parkinson's disease (PD), preliminary evidence indicates abnormal beta-phase coupling to gamma-amplitude in different brain areas, including the subthalamic nucleus (STN). We analyzed bilateral STN local field potentials (LFPs) in eight subjects with PD chronically implanted with deep brain stimulation electrodes during upright quiet standing and unperturbed walking. Phase-amplitude coupling (PAC) was computed using the Kullback-Liebler method, based on the modulation index. Neurophysiological recordings were correlated with clinical and kinematic measurements and individual molecular brain imaging studies ([123I]FP-CIT and single-photon emission computed tomography). We showed a dopamine-related increase in subthalamic beta-gamma PAC from standing to walking. Patients with poor PAC modulation and low PAC during walking spent significantly more time in the stance and double support phase of the gait cycle. Our results provide new insights into the subthalamic contribution to human gait and suggest cross-frequency coupling as a gateway mechanism to convey patient-specific information of motor control for human locomotion.

Somatosensory evoked potentials recorded from DBS electrodes: the origin of subcortical N18.

The different peaks of somatosensory-evoked potentials (SEP) originate from a variety of anatomical sites in the central nervous system. The origin of the median nerve subcortical N18 SEP has been studied under various conditions, but the exact site of its generation is still unclear. While it has been claimed to be located in the thalamic region, other studies indicated its possible origin below the pontomedullary junction. Here, we scrutinized and compared SEP recordings from median nerve stimulation through deep brain stimulation (DBS) electrodes implanted in various subcortical targets. We studied 24 patients with dystonia, Parkinson's disease, and chronic pain who underwent quadripolar electrode implantation for chronic DBS and recorded median nerve SEPs from globus pallidus internus (GPi), subthalamic nucleus (STN), thalamic ventral intermediate nucleus (Vim), and ventral posterolateral nucleus (VPL) and the centromedian-parafascicular complex (CM-Pf). The largest amplitude of the triphasic potential of the N18 complex was recorded in Vim. Bipolar recordings confirmed the origin to be close to Vim electrodes (and VPL/CM-Pf) and less close to STN electrodes. GPi recorded only far-field potentials in unipolar derivation. Recordings from DBS electrodes located in different subcortical areas allow determining the origin of certain subcortical SEP waves more precisely. The subcortical N18 of the median nerve SEP-to its largest extent-is generated ventral to the Vim in the region of the prelemniscal radiation/ zona incerta.

Effects of deep brain stimulation and verbal suggestions on pain in Parkinson's disease.

BACKGROUND AND OBJECTIVES: In Parkinson's disease (PD) patients, verbal suggestions have been shown to modulate motor and clinical outcomes in treatment with subthalamic deep brain stimulation (DBS). Furthermore, DBS may alleviate pain in PD. However, it is unknown if verbal suggestions influence DBS' effects on pain. METHODS: Twenty-four people with PD and DBS had stimulation downregulated (80-60 to 20%) and upregulated (from 20-60 to 80%) in a blinded manner on randomized test days: (1) with negative and positive suggestions of pain for down- and upregulation, respectively, and (2) with no suggestions to effect (control). Effects of DBS and verbal suggestions were assessed on ongoing and evoked pain (hypertonic saline injections) via 0-10 numerical rating scales along with motor symptoms, expectations, and blinding. RESULTS: Stimulation did not influence ongoing and evoked pain but influenced motor symptoms in the expected direction. Baseline and experimental pain measures showed no patterns in degree of pain. There was a trend toward negative suggestions increasing pain and positive suggestions decreasing pain. Results show significant differences in identical stimulation with negative vs positive suggestions (60% conditions AUC 38.75 vs 23.32, t(13) = 3.10, p < 0.001). Expectations to pain had small to moderate effects on evoked pain. Patients estimated stimulation level correctly within 10 points. CONCLUSION: Stimulation does not seem to influence ongoing and evoked pain, but verbal suggestions may influence pain levels. Patients appear to be unblinded to stimulation level which is an important consideration for future studies testing DBS in an attempted blind fashion.

Single neurons in the thalamus and subthalamic nucleus process cardiac and respiratory signals in humans.

Visceral signals are constantly processed by our central nervous system, enable homeostatic regulation, and influence perception, emotion, and cognition. While visceral processes at the cortical level have been extensively studied using non-invasive imaging techniques, very few studies have investigated how this information is processed at the single neuron level, both in humans and animals. Subcortical regions, relaying signals from peripheral interoceptors to cortical structures, are particularly understudied and how visceral information is processed in thalamic and subthalamic structures remains largely unknown. Here, we took advantage of intraoperative microelectrode recordings in patients undergoing surgery for deep brain stimulation (DBS) to investigate the activity of single neurons related to cardiac and respiratory functions in three subcortical regions: ventral intermedius nucleus (Vim) and ventral caudalis nucleus (Vc) of the thalamus, and subthalamic nucleus (STN). We report that the activity of a large portion of the recorded neurons (about 70%) was modulated by either the heartbeat, the cardiac inter-beat interval, or the respiration. These cardiac and respiratory response patterns varied largely across neurons both in terms of timing and their kind of modulation. A substantial proportion of these visceral neurons (30%) was responsive to more than one of the tested signals, underlining specialization and integration of cardiac and respiratory signals in STN and thalamic neurons. By extensively describing single unit activity related to cardiorespiratory function in thalamic and subthalamic neurons, our results highlight the major role of these subcortical regions in the processing of visceral signals.

Effects of subthalamic nucleus deep brain stimulation using different frequency programming paradigms on axial symptoms in advanced Parkinson's disease.

BACKGROUND: In advanced Parkinson's disease (PD), axial symptoms are common and can be debilitating. Although deep brain stimulation (DBS) significantly improves motor symptoms, conventional high-frequency stimulation (HFS) has limited effectiveness in improving axial symptoms. In this study, we investigated the effects on multiple axial symptoms after DBS surgery with three different frequency programming paradigms comprising HFS, low-frequency stimulation (LFS), and variable-frequency stimulation (VFS). METHODS: This study involved PD patients who had significant preoperative axial symptoms and underwent bilateral subthalamic nucleus (STN) DBS. Axial symptoms, motor symptoms, medications, and quality of life were evaluated preoperatively (baseline). One month after surgery, HFS was applied. At 6 months post-surgery, HFS assessments were performed, and HFS was switched to LFS. A further month later, we conducted LFS assessments and switched LFS to VFS. At 8 months after surgery, VFS assessments were performed. RESULTS: Of the 21 PD patients initially enrolled, 16 patients were ultimately included in this study. Regarding HFS, all axial symptoms except for the Berg Balance Scale (p < 0.0001) did not improve compared with the baseline (all p > 0.05). As for LFS and VFS, all axial symptoms improved significantly compared with both the baseline and HFS (all p < 0.05). Moreover, motor symptoms and medications were significantly better than the baseline (all p < 0.05) after using LFS and VFS. Additionally, the quality of life of the PD patients after receiving LFS and VFS was significantly better than at the baseline and with HFS (all p < 0.0001). CONCLUSION: Our findings indicate that HFS is ineffective at improving the majority of axial symptoms in advanced PD. However, both the LFS and VFS programming paradigms exhibit significant improvements in various axial symptoms.

Coupled Activation of the Hyperdirect and Cerebellothalamic Pathways with Zona Incerta Deep Brain Stimulation.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or ventral intermediate nucleus (VIM) are established targets for the treatment of Parkinson's disease (PD) or essential tremor (ET), respectively. However, DBS of the zona incerta (ZI) can be effective for both disorders. VIM DBS is assumed to achieve its therapeutic effect via activation of the cerebellothalamic (CBT) pathway, whereas the activation of the hyperdirect (HD) pathway likely plays a role in the mechanisms of STN DBS. Interestingly, HD pathway axons also emit collaterals to the ZI and red nucleus (RN) and the CBT pathway courses nearby to the ZI. OBJECTIVE: The aim was to examine the ability of ZI DBS to mutually activate the HD and CBT pathways in a detailed computational model of human DBS. METHODS: We extended a previous model of the human HD pathway to incorporate axon collaterals to the ZI and RN. The anatomical framework of the model system also included representations of the CBT pathway and internal capsule (IC) fibers of passage. We then performed detailed biophysical simulations to quantify DBS activation of the HD, CBT, and IC pathways with electrodes located in either the STN or ZI. RESULTS: STN DBS and ZI DBS both robustly activated the HD pathway. However, STN DBS was limited by IC activation at higher stimulus amplitudes. Alternatively, ZI DBS avoided IC activation while simultaneously activating the HD and CBT pathways. CONCLUSIONS: From both neuroanatomical and biophysical perspectives, ZI DBS represents an advantageous target for coupled activation of the HD and CBT pathways. © 2024 International Parkinson and Movement Disorder Society.

7-Tesla Magnetic Resonance Imaging Scanning in Deep Brain Stimulation for Parkinson's Disease: Improving Visualization of the Dorsolateral Subthalamic Nucleus.

BACKGROUND: Identifying the dorsolateral subthalamic nucleus (STN) for deep brain stimulation (DBS) in Parkinson's disease (PD) can be challenging due to the size and double-oblique orientation. Since 2015 we implemented 7-Tesla T2 weighted magnetic resonance imaging (7 T T2) for improving visualization and targeting of the dorsolateral STN. We describe the changes in surgical planning and outcome since implementation of 7 T T2 for DBS in PD. METHODS: By comparing two cohorts of STN DBS patients in different time periods we evaluated the influence of 7 T T2 on STN target planning, the number of microelectrode recording (MER) trajectories, length of STN activity and the postoperative motor (UPDRS) improvement. RESULTS: From February 2007 to January 2014, 1.5 and 3-Tesla T2 guided STN DBS with 3 MER channels was performed in 76 PD patients. Average length of recorded STN activity in the definite electrode trajectory was 3.9 ± 1.5 mm. From January 2015 to January 2022 7 T T2 and MER-guided STN DBS was performed in 182 PD patients. Average length of recorded STN activity in the definite electrode trajectory was 5.1 ± 1.3 mm and used MER channels decreased from 3 to 1. Average UPDRS improvement was comparable. CONCLUSION: Implementation of 7 T T2 for STN DBS enabled a refinement in targeting. Combining classical DBS targeting with dorsolateral STN alignment may be used to determine the optimal trajectory. The improvement in dorsolateral STN visualization can be used for further target refinements, for example adding probabilistic subthalamic connectivity, to enhance clinical outcome of STN DBS.

Estimation of the transmission delays in the basal ganglia of the macaque monkey and subsequent predictions about oscillatory activity under dopamine depletion.

The timescales of the dynamics of a system depend on the combination of the timescales of its components and of its transmission delays between components. Here, we combine experimental stimulation data from 10 studies in macaque monkeys that reveal the timing of excitatory and inhibitory events in the basal ganglia circuit, to estimate its set of transmission delays. In doing so, we reveal possible inconsistencies in the existing data, calling for replications, and we propose two possible sets of transmission delays. We then integrate these delays in a model of the primate basal ganglia that does not rely on direct and indirect pathways' segregation and show that extrastriatal dopaminergic depletion in the external part of the globus pallidus and in the subthalamic nucleus is sufficient to generate ß-band oscillations (in the high part, 20-35 Hz, of the band). More specifically, we show that D2 and D5 dopamine receptors in these nuclei play opposing roles in the emergence of these oscillations, thereby explaining how completely deactivating D5 receptors in the subthalamic nucleus can, paradoxically, cancel oscillations.

Nonlinear effects at the electrode-tissue interface of deep brain stimulation electrodes.

Objective.The electrode-tissue interface provides the critical path for charge transfer in neurostimulation therapies and exhibits well-established nonlinear properties at high applied currents or voltages. These nonlinear properties may influence the efficacy and safety of applied stimulation but are typically neglected in computational models. In this study, nonlinear behavior of the electrode-tissue interface impedance was incorporated in a computational model of deep brain stimulation (DBS) to simulate the impact on neural activation and safety considerations.Approach.Nonlinear electrode-tissue interface properties were incorporated in a finite element model of DBS electrodesin vitroandin vivo,in the rat subthalamic nucleus, using an iterative approach. The transition point from linear to nonlinear behavior was determined for voltage and current-controlled stimulation. Predicted levels of neural activation during DBS were examined and the region of linear operation of the electrode was compared with the Shannon safety limit.Main results.A clear transition of the electrode-tissue interface impedance to nonlinear behavior was observed for both current and voltage-controlled stimulation. The transition occurred at lower values of activation overpotential for simulatedin vivothanin vitroconditions (91 mV and 165 mV respectively for current-controlled stimulation; 110 mV and 275 mV for voltage-controlled stimulation), corresponding to an applied current of 30µA and 45µA, or voltage of 330 mV at 1 kHz. The onset of nonlinearity occurred at lower values of the overpotential as frequency was increased. Incorporation of nonlinear properties resulted in activation of a higher proportion of neurons under voltage-controlled stimulation. Under current-controlled stimulation, the predicted transition to nonlinear behavior and Faradaic charge transfer at stimulation amplitudes of 30µA, corresponds to a charge density of 2.29µC cm-2and charge of 1.8 nC, well-below the Shannon safety limit.Significance.The results indicate that DBS electrodes may operate within the nonlinear region at clinically relevant stimulation amplitudes. This affects the extent of neural activation under voltage-controlled stimulation and the transition to Faradaic charge transfer for both voltage- and current-controlled stimulation with important implications for targeting of neural populations and the design of safe stimulation protocols.

Detection of evoked resonant neural activity in Parkinson's disease.

Objective. This study investigated a machine-learning approach to detect the presence of evoked resonant neural activity (ERNA) recorded during deep brain stimulation (DBS) of the subthalamic nucleus (STN) in people with Parkinson's disease.Approach. Seven binary classifiers were trained to distinguish ERNA from the background neural activity using eight different time-domain signal features.Main results. Nested cross-validation revealed a strong classification performance of 99.1% accuracy, with 99.6% specificity and 98.7% sensitivity to detect ERNA. Using a semi-simulated ERNA dataset, the results show that a signal-to-noise ratio of 15 dB is required to maintain a 90% classifier sensitivity. ERNA detection is feasible with an appropriate combination of signal processing, feature extraction and classifier. Future work should consider reducing the computational complexity for use in real-time applications.Significance. The presence of ERNA can be used to indicate the location of a DBS electrode array during implantation surgery. The confidence score of the detector could be useful for assisting clinicians to adjust the position of the DBS electrode array inside/outside the STN.

Overlapping stimulation of subthalamic nucleus and dentato-rubro-thalamic tract in Parkinson's disease after deep brain stimulation.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces tremor, rigidity, and akinesia. According to the literature, the dentato-rubro-thalamic tract (DRTt) is verified target for DBS in essential tremor; however, its role in the treatment of Parkinson's disease is only vaguely described. The aim of our study was to identify the relationship between symptom alleviation in PD patients and the distance of the DBS electrode electric field (EF) to the DRTt. METHODS: A single-center retrospective analysis of patients (N = 30) with idiopathic Parkinson's disease (PD) who underwent DBS between November 2018 and January 2020 was performed. DRTt and STN were visualized using diffusion-weighted imaging (DWI) and tractography protocol of magnetic resonance (MR). The EF was calculated and compared with STN and course of DRTt. Evaluation of patients before and after surgery was performed with use of UPDRS-III scale. The association between distance from EF to DRTt and clinical outcomes was examined. To confirm the anatomical variation between DRTt and STN observed in tractography, white matter dissection was performed with the Klingler technique on ten human brains. RESULTS: Patients with EF overlapping STN and DRTt benefited from significant motor symptoms improvement. Anatomical findings confirmed the presence of population differences in variability of the DRTt course and were consistent with the DRTt visualized by MR. CONCLUSIONS: DRTt proximity to STN, the main target in PD DBS surgery, confirmed by DWI with tractography protocol of MR combined with proper predefined stimulation parameters may improve efficacy of DBS-STN.

Spatiotemporal signal space separation for regions of interest: Application for extracting neuromagnetic responses evoked by deep brain stimulation.

Magnetoencephalography (MEG) recordings are often contaminated by interference that can exceed the amplitude of physiological brain activity by several orders of magnitude. Furthermore, the activity of interference sources may spatially extend (known as source leakage) into the activity of brain signals of interest, resulting in source estimation inaccuracies. This problem is particularly apparent when using MEG to interrogate the effects of brain stimulation on large-scale cortical networks. In this technical report, we develop a novel denoising approach for suppressing the leakage of interference source activity into the activity representing a brain region of interest. This approach leverages spatial and temporal domain projectors for signal arising from prespecified anatomical regions of interest. We apply this denoising approach to reconstruct simulated evoked response topographies to deep brain stimulation (DBS) in a phantom recording. We highlight the advantages of our approach compared to the benchmark-spatiotemporal signal space separation-and show that it can more accurately reveal brain stimulation-evoked response topographies. Finally, we apply our method to MEG recordings from a single patient with Parkinson's disease, to reveal early cortical-evoked responses to DBS of the subthalamic nucleus.

NIH Toolbox performance of persons with Parkinson's disease according to GBA1 and STN-DBS status.

OBJECTIVE: Mutations in the glucocerebrosidase (GBA1) gene and subthalamic nucleus deep brain stimulation (STN-DBS) are independently associated with cognitive dysfunction in persons with Parkinson's disease (PwP). We hypothesized that PwP with both GBA1 mutations and STN-DBS are at greater risk of cognitive dysfunction than PwP with only GBA1 mutations or STN-DBS, or neither. In this study, we determined the pattern of cognitive dysfunction in PwP based on GBA1 mutation status and STN-DBS treatment. METHODS: PwP who are GBA1 mutation carriers with or without DBS (GBA1+DBS+, GBA1+DBS-), and noncarriers with or without DBS (GBA1-DBS+, GBA1-DBS-) were included. Using the NIH Toolbox, cross-sectional differences in response inhibition, processing speed, and episodic memory were compared using analysis of variance with adjustment for relevant covariates. RESULTS: Data were available for 9 GBA1+DBS+, 14 GBA1+DBS-, 17 GBA1-DBS+, and 26 GBA1-DBS- PwP. In this cross-sectional study, after adjusting for covariates, we found that performance on the Flanker test (measure of response inhibition) was lower in GBA1+DBS+ PwP compared with GBA1-DBS+ PwP (P = 0.030). INTERPRETATION: PwP who carry GBA1 mutations and have STN-DBS have greater impaired response inhibition compared with PwP with STN-DBS but without GBA1 mutations. Longitudinal data, including preoperative scores, are required to definitively determine whether GBA1 mutation carriers respond differently to STN-DBS, particularly in the domain of response inhibition.

Mapping Subcortico-Cortical Coupling-A Comparison of Thalamic and Subthalamic Oscillations.

BACKGROUND: The ventral intermediate nucleus of the thalamus (VIM) is an effective target for deep brain stimulation in tremor patients. Despite its therapeutic importance, its oscillatory coupling to cortical areas has rarely been investigated in humans. OBJECTIVES: The objective of this study was to identify the cortical areas coupled to the VIM in patients with essential tremor. METHODS: We combined resting-state magnetoencephalography with local field potential recordings from the VIM of 19 essential tremor patients. Whole-brain maps of VIM-cortex coherence in several frequency bands were constructed using beamforming and compared with corresponding maps of subthalamic nucleus (STN) coherence based on data from 19 patients with Parkinson's disease. In addition, we computed spectral Granger causality. RESULTS: The topographies of VIM-cortex and STN-cortex coherence were very similar overall but differed quantitatively. Both nuclei were coupled to the ipsilateral sensorimotor cortex in the high-beta band; to the sensorimotor cortex, brainstem, and cerebellum in the low-beta band; and to the temporal cortex, brainstem, and cerebellum in the alpha band. High-beta coherence to sensorimotor cortex was stronger for the STN (P = 0.014), whereas low-beta coherence to the brainstem was stronger for the VIM (P = 0.017). Although the STN was driven by cortical activity in the high-beta band, the VIM led the sensorimotor cortex in the alpha band. CONCLUSIONS: Thalamo-cortical coupling is spatially and spectrally organized. The overall similar topographies of VIM-cortex and STN-cortex coherence suggest that functional connections are not necessarily unique to one subcortical structure but might reflect larger frequency-specific networks involving VIM and STN to a different degree. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Interleaved Propofol-Ketamine Maintains DBS Physiology and Hemodynamic Stability: A Double-Blind Randomized Controlled Trial.

BACKGROUND: The gold standard anesthesia for deep brain stimulation (DBS) surgery is the "awake" approach, using local anesthesia alone. Although it offers high-quality microelectrode recordings and therapeutic-window assessment, it potentially causes patients extreme stress and might result in suboptimal surgical outcomes. General anesthesia or deep sedation is an alternative, but may reduce physiological testing reliability and lead localization accuracy. OBJECTIVES: The aim is to investigate a novel anesthesia regimen of ketamine-induced conscious sedation for the physiological testing phase of DBS surgery. METHODS: Parkinson's patients undergoing subthalamic DBS surgery were randomly divided into experimental and control groups. During physiological testing, the groups received 0.25 mg/kg/h ketamine infusion and normal saline, respectively. Both groups had moderate propofol sedation before and after physiological testing. The primary outcome was recording quality. Secondary outcomes included hemodynamic stability, lead accuracy, motor and cognitive outcome, patient satisfaction, and adverse events. RESULTS: Thirty patients, 15 from each group, were included. Intraoperatively, the electrophysiological signature and lead localization were similar under ketamine and saline. Tremor amplitude was slightly lower under ketamine. Postoperatively, patients in the ketamine group reported significantly higher satisfaction with anesthesia. The improvement in Unified Parkinson's disease rating scale part-III was similar between the groups. No negative effects of ketamine on hemodynamic stability or cognition were reported perioperatively. CONCLUSIONS: Ketamine-induced conscious sedation provided high quality microelectrode recordings comparable with awake conditions. Additionally, it seems to allow superior patient satisfaction and hemodynamic stability, while maintaining similar post-operative outcomes. Therefore, it holds promise as a novel alternative anesthetic regimen for DBS. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Association of emotional and behavioral problems with the development of the substantia nigra, subthalamic nucleus, and red nucleus volumes and asymmetries from childhood to adolescence: A longitudinal cohort study.

The substantia nigra (SN), subthalamic nucleus (STN), and red nucleus (RN) have been widely studied as important biomarkers of degenerative diseases. However, how they develop in childhood and adolescence and are affected by emotional behavior has not been studied thus far. This population-based longitudinal cohort study used data from a representative sample followed two to five times. Emotional and behavioral problems were assessed with the Strengths and Difficulties Questionnaire (SDQ). Linear mixed models were used to map developmental trajectories and behavioral regulation. Using an innovative automated image segmentation technique, we quantified the volumes and asymmetries of the SN, STN and RN with 1226 MRI scans of a large longitudinal sample of 667 subjects aged 6-15 years and mapped their developmental trajectories. The results showed that the absolute and relative volumes of the bilateral SN and right STN showed linear increases, while the absolute volume of the right RN and relative volume of the bilateral RN decreased linearly, these effects were not affected by gender. Hyperactivity/inattention weakened the increase in SN volume and reduced the absolute volume of the STN, conduct problems impeded the RN volume from decreasing, and emotional symptoms changed the direction of SN lateralization. This longitudinal cohort study mapped the developmental trajectories of SN, STN, and RN volumes and asymmetries from childhood to adolescence, and found the association of emotional symptoms, conduct problems, and hyperactivity/inattention with these trajectories, providing guidance for preventing and intervening in cognitive and emotional behavioral problems.

Restless legs syndrome in the dominant Parkinson's side related to subthalamic deep-brain stimulation.

BACKGROUND: Restless legs syndrome (RLS) has an increased estimated prevalence in patients with Parkinson's disease (PS). RLS frequently mimics symptoms intrinsic to PD, such as motor restlessness, contributing to making its diagnosis challenging in this population. We report the case of a patient with new-onset RLS following subthalamic deep-brain stimulation (DBS-STN). We assessed symptoms using suggested immobilization test (SIT) with both DBS-STN activated and switched off. CASE DESCRIPTION: A 59-year-old man with idiopathic PD developed disabling RLS following DBS-STN at age 58, with PD onset at 50 manifesting as left arm tremor. Despite improved motor symptoms during the month following surgery, the patient experienced left leg discomfort at rest, transiently alleviated by movements due to an irrepressible urge to move, and worsened at night. Symptoms had no temporal relationship with oral dopa-therapy and disappeared when DBS-STN was deactivated. A 1 h SIT assessed motor behavior with irrepressible urge to move, as well as sensory symptoms by visual analog scale. After 30 m DBS-STN was switched off followed by the appearance of tremor in the left arm while both motor and sensory symptoms of RLS disappeared in the left leg. DISCUSSION: The mechanisms of DBS-STN's impact on RLS remain controversial. We hypothesize the DBS-STN to induce in our patient a hyperdopaminergic tone. DBS-induced and DBS-ameliorated RLS represent interesting conditions to further understand the pathophysiology of RLS. Moreover, the present observation suggests that SIT can be a valuable tool to assess RLS in PD patients before and after DBS-STN in future prospective studies.