Parkinson\'s disease (PD) ranks as the second most prevalent and rapidly growing neurodegenerative disorder. As a primary output nucleus within the basal ganglia (BG), the globus pallidus interna (GPi) is a key structure in BG information processing. It is also a key target for deep brain stimulation (DBS) to alleviate motor symptoms of PD. Previous studies have identifiedPD patients exhibiting abnormal neuronal activity in the GPi. On the other hand, various types of dopamine receptor (DR)-positive neurons have been identified within the GPi. However, the electrophysiological properties of specific DR-positive neurons within the GPi and their alterations in PD have not been addressed. In the present study, we used whole-cell patch-clamp recordings to identify two neuronal subpopulations within the GPi, dopamine D1 receptor (D1R)-positive, and dopamine D2 receptor (D2R)-positive neurons, which exhibited distinct electrophysiological properties. Additionally, significant alterations of electrophysiological properties of D2R-positive neurons within the GPi were observed in 6-hydroxydopamine (6-OHDA)-lesioned mice. These data suggest that the distinct electrophysiological properties of specific DR-positive neurons and their abnormal alteration in the GPi may be associated with PD\'s pathogenesis.

UNASSIGNED: Subthalamic nucleus (STN) and globus pallidus interna (GPi) are two main structures primarily targeted by deep brain stimulation (DBS) to treat advanced Parkinson\'s disease (PD). A subset of cases with unsatisfactory outcomes may benefit from rescue DBS surgery targeting another structure, while these patients\' characteristics have not been well described and this phenomenon has not been well reviewed.
UNASSIGNED: This monocentric retrospective study included patients with PD, who underwent rescue STN DBS following an unsatisfactory outcome of the initial bilateral GPi DBS in a retrospective manner. A short review of the current literature was conducted to report the clinical outcome of rescue DBS surgeries.
UNASSIGNED: Eight patients were identified, and six of them were included in this study. The rescue STN DBS was performed 19.8 months after the initial GPi DBS. After 8.8 months from the rescue STN DBS, patients showed a significant off-medication improvement by 29.2% in motor symptoms compared to initial GPi DBS. Non-motor symptoms and the health-related quality of life were also significantly improved.
UNASSIGNED: Our findings suggest that the rescue STN DBS may improve off-medication motor and non-motor symptoms and quality of life in patients with failure of initial GPi DBS. The short review of the current literature showed that the target switching from GPi to STN was mainly due to poor initial outcomes and was performed by target substitution, whereas the switching from STN to GPi was mainly due to a gradual waning of benefits, long-term axial symptoms, dyskinesia, and dystonia and was performed by target addition.

[This corrects the article DOI: 10.3389/fnhum.2021.604433.].

UNASSIGNED: Cerebral palsy (CP), a complex syndrome with multiple etiologies, is characterized by a range of movement disorders within the hypokinetic and hyperkinetic spectrum (dystonia or choreoathetosis). CP is often accompanied by neurological and psychiatric signs, such as spasticity, ataxia, and cognitive disorders. Although current treatment options for CP include pharmacological interventions, rehabilitation programs, and spasticity relief surgery, their effectiveness remains limited. Deep brain stimulation (DBS) has demonstrated significant effectiveness in managing dyskinesia; however, its potential therapeutic effect on CP remains determined.
UNASSIGNED: We present a case of a 44-year-old Asian female who was born as a twin with neonatal ischemic-hypoxic encephalopathy due to prolonged labor and delivery. She was diagnosed with CP at the age of 1 year. The patient exhibited delayed development compared to her peers and presented with various symptoms, including slurred speech, broad-based gait, horseshoe inversion of the right lower extremity, involuntary shaking of the upper extremities bilaterally, and hypotonia and showed no improvement with levodopa therapy. Two years ago, she developed progressive head tremors, which worsened during periods of tension and improved during sleep. As medical treatments proved ineffective and there were no contraindications to surgery, we performed bilateral globus pallidus interna DBS (GPi-DBS) to alleviate her motor dysfunction.
UNASSIGNED: Following a 6-month follow-up, the patient demonstrated significant improvements in motor symptoms, including head and limb tremors and dystonia. In addition, significant improvement was observed in her overall psychological well-being, as evidenced by reduced anxiety and depression levels.
UNASSIGNED: DBS is an effective treatment for dyskinesia symptoms associated with CP in adults. Moreover, its effectiveness may continue to increase over time.

UNASSIGNED: We aimed to compare the motor effect of bilateral globus pallidus interna (GPi) deep brain stimulation (DBS) on motor subtypes of Parkinson\'s disease (PD) patients and identify preoperative predictive factors of short-term motor outcome.
UNASSIGNED: We retrospectively investigated bilateral GPi DBS clinical outcomes in 55 PD patients in 1 year follow up. Motor outcome was measured by the Movement Disorder Society Unified Parkinson\'s Disease Rating Scale (MDS-UPDRS) part III before and 1 year after surgery. Clinical outcomes were compared among different motor subtypes. Preoperative predictors of motor outcome were assessed by performing univariate and multivariate linear regression and logistic regression analyses.
UNASSIGNED: At 1 year following implantation, GPi DBS significantly improved the off-medication MDS-UPDRS III scores in all motor subtype cohorts, with prominent improvement in tremor. No significant difference of postoperative motor symptoms changes was found except greater tremor improvement achieved in both the tremor-dominant (TD) and indeterminate (IND) patients compared to the postural instability and gait difficulty (PIGD) patients. High percentage of PIGD patients were weak responders to DBS. Better levodopa responsiveness and more severe tremor predicted greater overall improvement of motor function in the entire cohort. Similarly, both levodopa responsiveness and tremor improvement were confirmed as predictors for motor improvement in PIGD patients.
UNASSIGNED: Bilateral GPi DBS could effectively improve motor outcomes in PD patients regardless of motor subtypes. Both TD and IND patients obtained larger tremor improvement. The intensity of levodopa responsiveness and the severity of tremor could serve as predictors of motor improvement 1 year after GPi DBS.

BACKGROUND: The up-to-date literature systematically reviewing the predictive value of preoperative levodopa responsiveness after deep brain stimulation (DBS) surgery in motor outcomes in Parkinson\'s disease (PD) is lacking.
OBJECTIVE: To address this issue in patients with PD undergoing bilateral subthalamic nucleus (STN) or globus pallidus interna (GPi) DBS.
METHODS: We used the existing PRISMA consensus statement. A comprehensive review of literature from 1993 to May 2021 retrieved from PubMed was conducted.
RESULTS: The STN-DBS responsiveness was significantly correlated with the preoperative levodopa responsiveness for the total score of UPDRS-III at both 6- and 12-month follow-ups (P < 0.001). Such correlations were significant after controlling for age at time of surgery and disease duration. The significance of correlation disappeared for longer follow-up times. For the sub-scores of UPDRS-III, a significant correlation between the preoperative levodopa responsiveness and STN DBS responsiveness was observed for rigidity, bradykinesia, and axial symptoms, but not for tremor (P = 0.002, 0.010, 0.007, and 0.542, respectively). The preoperative levodopa responsiveness was significantly correlated with GPi DBS responsiveness for the UPDRS-III total score at a median follow-up of 12 months (P = 0.030).
CONCLUSIONS: The current study confirmed the value of preoperative levodopa responsiveness for prediction of the short-term motor outcome after DBS (for both STN and GPi). The predictive value of levodopa responsiveness in short-term outcomes for respective cardinal motor disabilities and the loss of its predictive value after STN DBS for long-term motor outcomes were highlighted by this study.

BACKGROUND: Previous studies have shown that subthalamic nucleus (STN) and unilateral globus pallidus interna (GPi) are similarly effective in the deep brain stimulation (DBS) treatment of motor symptoms. However, the counterintuitively more common clinical application of STN DBS makes us hypothesize that STN is superior to GPi in the treatment of motor symptoms.
METHODS: In this prospective, double-blind, randomized crossover study, idiopathic PD patients treated with combined unilateral STN and contralateral GPi DBS (STN in one brain hemisphere and GPi in the other) for 2 to 3 years were enrolled. The MDS UPDRS-III total score and subscale scores for axial and bilateral limb symptoms were assessed preoperatively and at 2- to 3-year follow-up in four randomized, double-blinded conditions: (1) Med-STN+GPi-, (2) Med-STN-GPi+, (3) Med+STN+GPi-, and (4) Med+STN-GPi+.
RESULTS: Eight patients had completed 30 trials of assessment. Compared with the preoperative Med- state, in the Med-STN+GPi- condition, the cardinal symptoms in both sides of the body were all improved. In the Med-STN-GPi+ condition, symptoms of the GPi-stim limb were improved, while only tremor was improved on the ipsilateral side, although all axial symptoms showed aggravation. Compared with the preoperative Med+ state, in the Med+STN+GPi- state, cardinal symptoms were improved on both sides, except that tremor was worsened on the STN-stim side. In the Med+STN-GPi+ state, the overall motor symptoms were aggravated compared with the preoperative Med+ state. Most axial symptoms worsened at acute unilateral STN or GPi DBS onset, compared to both preoperative Med- and Med+ states. No side effects associated with this study were seen.
CONCLUSIONS: Improvement in motor symptoms was greater in all sub-scores favoring STN. The effects of STN+ were seen on both sides of the body, while GPi+ mainly acted on the contralateral side.

The subthalamic nucleus (STN) is one of the best targets for therapeutic deep brain stimulation (DBS) to control motor symptoms in Parkinson\'s disease. However, the precise circuitry underlying the effects of STN-DBS remains unclear. To understand how electrical stimulation affects STN projection neurons, we used a retrograde viral vector (AAV-retro-hSyn-eGFP) to label STN neurons projecting to the substantia nigra pars reticulata (SNr) (STN-SNr neurons) or the globus pallidus interna (GPi) (STN-GPi neurons) in mice, and performed whole-cell patch-clamp recordings from these projection neurons in ex vivo brain slices. We found that STN-SNr neurons exhibited stronger responses to depolarizing stimulation than STN-GPi neurons. In most STN-SNr and STN-GPi neurons, inhibitory synaptic inputs predominated over excitatory inputs and electrical stimulation at 20-130 Hz inhibited these neurons in the short term; its longer-term effects varied. 6-OHDA lesion of the nigrostriatal dopaminergic pathway significantly reduced inhibitory synaptic inputs in STN-GPi neurons, but did not change synaptic inputs in STN-SNr neurons; it enhanced short-term electrical-stimulation-induced inhibition in STN-SNr neurons but reversed the effect of short-term electrical stimulation on the firing rate in STN-GPi neurons from inhibitory to excitatory; in both STN-SNr and STN-GPi neurons, it increased the inhibition but attenuated the enhancement of firing rate induced by long-term electrical stimulation. Our results suggest that STN-SNr and STN-GPi neurons differ in their synaptic inputs, their responses to electrical stimulation, and their modification under parkinsonian conditions; STN-GPi neurons may play important roles in both the pathophysiology and therapeutic treatment of Parkinson\'s disease.

Objective: To investigate the correlation between preoperative response to the L-dopa challenge test and efficacy of deep brain stimulation (DBS) on motor function in Parkinson\'s disease (PD). Methods: We retrospectively reviewed the data of 38 patients with idiopathic PD who underwent DBS surgery with a median follow-up duration of 7 months. Twenty underwent bilateral globus pallidus interna (GPi) DBS, and 18 underwent bilateral subthalamic nucleus (STN) DBS. The Movement Disorder Society Unified Parkinson Disease Rating Scale-Motor Part (MDS UPDRS-III) was assessed before surgery and at the last follow-up in different medication and stimulation conditions, respectively. Results: Pearson\'s correlation analysis revealed a positive correlation between preoperative L-dopa challenge responsiveness and GPi-DBS responsiveness on the total score (R 2 = 0.283, p = 0.016) but not on the non-tremor total score (R 2 = 0.158, p = 0.083) of MDS UPDRS-III. Such correlation remained significant (R 2\' = 0.332, p = 0.010) after controlling for age at the time of surgery as confounding factor by partial correlation analysis. The preoperative L-dopa challenge responsiveness was significantly correlated with the tremor-controlling outcome of GPi-DBS (R 2 = 0.390, p = 0.003). In contrast, we found a positive correlation between preoperative L-dopa challenge responsiveness and STN-DBS responsiveness on the non-tremor total score (R 2 = 0.290, p = 0.021), but not on the total score (R 2 = 0.130, p = 0.141) of MDS UPDRS-III. The partial correlation analysis further demonstrated that the predictive value of preoperative L-dopa challenge responsiveness on the non-tremor motor outcome of STN-DBS was eliminated (R 2\' = 0.120, p = 0.174) after controlling for age at the time of surgery as confounding factor. Interpretation: The short-term predictive value of preoperative response to the L-dopa challenge test for the motor outcome of GPi-DBS in PD was systematically described. Our findings suggest: (1) a solid therapeutic effect of GPi-DBS in treating L-dopa-responsive tremors; (2) a negative effect of age at the time of surgery on motor outcomes of STN-DBS, (3) a possible preference of STN- to GPi-DBS in L-dopa-resistant tremor control, and (4) a possible preference of GPi- to STN-DBS in elderly PD patients who have a satisfactory dopamine response.

Deep brain stimulation (DBS) has become a widely performed surgical procedure for patients with medically refractory movement disorders and mental disorders. It is clinically important to set up a MRI protocol to map the brain targets and electrodes of the patients before and after DBS and to understand the imaging artifacts caused by the electrodes.
Five patients with DBS electrodes implanted in the habenula (Hb), fourteen patients with globus pallidus internus (GPi) targeted DBS, three pre-DBS patients and seven healthy controls were included in the study. The MRI protocol consisted of magnetization prepared rapid acquisition gradient echo T1 (MPRAGE T1W), 3D multi-echo gradient recalled echo (ME-GRE) and 2D fast spin echo T2 (FSE T2W) sequences to map the brain targets and electrodes of the patients. Phantom experiments were also run to determine both the artifacts and the susceptibility of the electrodes. Signal to noise ratio (SNR) on T1W, T2W and GRE datasets were measured. The visibility of the brain structures was scored according to the Rose criterion. A detailed analysis of the characteristics of the electrodes in all three sequence types was performed to confirm the reliability of the postoperative MRI approach. In order to understand the signal behavior, we also simulated the corresponding magnitude data using the same imaging parameters as in the phantom sequences.
The mean ± inter-subject variability of the SNRs, across the subjects for T1W, T2W, and GRE datasets were 20.1 ± 8.1, 14.9 ± 3.2, and 43.0 ± 7.6, respectively. High resolution MPRAGE T1W and FSE T2W data both showed excellent contrast for the habenula and were complementary to each other. The mean visibility of the habenula in the 25 cases for the MPRAGE T1W data was 5.28 ± 1.11; and the mean visibility in the 20 cases for the FSE T2W data was 5.78 ± 1.30. Quantitative susceptibility mapping (QSM), reconstructed from the ME-GRE sequence, provided sufficient contrast to distinguish the substructures of the globus pallidus. The susceptibilities of the GPi and globus pallidus externa (GPe) were 0.087 ± 0.013 ppm and 0.115 ± 0.015 ppm, respectively. FSE T2W sequences provided the best image quality with smallest image blooming of stimulator leads compared to MPRAGE T1W images and GRE sequence images, the measured diameters of electrodes were 1.91 ± 0.22, 2.77 ± 0.22, and 2.72 ± 0.20 mm, respectively. High resolution, high bandwidth and short TE (TE = 2.6 ms) GRE helped constrain the artifacts to the area of the electrodes and the dipole effect seen in the GRE filtered phase data provided an effective mean to locate the end of the DBS lead.
The imaging protocol consisting of MPRAGE T1W, FSE T2W and ME-GRE sequences provided excellent pre- and post-operative visualization of the brain targets and electrodes for patients undergoing DBS treatment. Although the artifacts around the electrodes can be severe, sometimes these same artifacts can be useful in identifying their location.