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Aims: The effects of subthalamic nucleus (STN)-deep brain stimulation (DBS) on brain topological metrics, functional connectivity (FC), and white matter integrity were studied in levodopa-treated Parkinson's disease (PD) patients before and after DBS., Methods: Clinical assessment, resting-state functional MRI (rs-fMRI), and diffusion tensor imaging (DTI) were performed pre- and post-DBS in 15 PD patients, using a within-subject design. The rs-fMRI identified brain network topological metric and FC changes using graph-theory- and seed-based methods. White matter integrity was determined by DTI and tract-based spatial statistics., Results: Unified Parkinson's Disease Rating Scale III (UPDRS- III) scores were significantly improved by 35.3% (p < 0.01) after DBS in PD patients, compared with pre-DBS patients without medication. Post-DBS PD patients showed a significant decrease in the graph-theory-based degree and cost in the middle temporal gyrus and temporo-occipital part-Right. Changes in FC were seen in four brain regions, and a decrease in white matter integrity was seen in the left anterior corona radiata. The topological metrics changes were correlated with Beck Depression Inventory II (BDI-II) and the FC changes with UPDRS-III scores., Conclusion: STN-DBS modulated graph-theoretical metrics, FC, and white matter integrity. Brain connectivity changes observed with multi-modal imaging were also associated with postoperative clinical improvement. These findings suggest that the effects of STN-DBS are caused by brain network alterations., (© 2021 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: General anesthetics-induced changes of electrical oscillations in the basal ganglia may render the identification of the stimulation targets difficult. The authors hypothesized that while sevoflurane anesthesia entrains coherent lower frequency oscillations, it does not affect the identification of the subthalamic nucleus and clinical outcome., Methods: A cohort of 19 patients with Parkinson's disease with comparable disability underwent placement of electrodes under either sevoflurane general anesthesia (n = 10) or local anesthesia (n = 9). Microelectrode recordings during targeting were compared for neuronal spiking characteristics and oscillatory dynamics. Clinical outcomes were compared at 5-yr follow-up., Results: Under sevoflurane anesthesia, subbeta frequency oscillations predominated (general vs. local anesthesia, mean ± SD; delta: 13 ± 7.3% vs. 7.8 ± 4.8%; theta: 8.4 ± 4.1% vs. 3.9 ± 1.6%; alpha: 8.1 ± 4.1% vs. 4.8 ± 1.5%; all P < 0.001). In addition, distinct dorsolateral beta and ventromedial gamma oscillations were detected in the subthalamic nucleus solely in awake surgery (mean ± SD; dorsal vs. ventral beta band power: 20.5 ± 6.6% vs. 15.4 ± 4.3%; P < 0.001). Firing properties of subthalamic neurons did not show significant difference between groups. Clinical outcomes with regard to improvement in motor and psychiatric symptoms and adverse effects were comparable for both groups. Tract numbers of microelectrode recording, active contact coordinates, and stimulation parameters were also equivalent., Conclusions: Sevoflurane general anesthesia decreased beta-frequency oscillations by inducing coherent lower frequency oscillations, comparable to the pattern seen in the scalp electroencephalogram. Nevertheless, sevoflurane-induced changes in electrical activity patterns did not reduce electrode placement accuracy and clinical effect. These observations suggest that microelectrode-guided deep brain stimulation under sevoflurane anesthesia is a feasible clinical option.

Acute (e.g., traumatic brain injury or stroke) and chronic (e.g., dementia or Parkinson's disease dementia) neurological disorders that involve cognitive impairment and dysfunctional neural circuits always lead to a dreadful and costly experience for patients and their families. The application of deep brain stimulation for the treatment of neuropsychiatric disorders has shown great potential to modulate pathological neural circuits and trigger endogenous neurogenesis. We summarize several important clinical and translational studies that utilize deep brain stimulation to improve cognition based on the potentiation of neural plasticity and neurogenesis. In addition, we discuss the neuroanatomy and cerebral circuits implicated in such studies as well as the potential mechanisms underlying therapeutic benefits.

Rational: The therapeutic effect of deep brain stimulation (DBS) for refractory obsessive-compulsive disorder (OCD) has been studied, but complications after this treatment have rarely been noted., Patient Concerns: A 28-year-old man with treatment-resistant OCD received bilateral ventral capsule/ventral striatum stimulation for 12 months., Diagnosis: Compulsive skin-picking behavior and infection were noted following 12-month DBS treatment., Intervention: We removed the implanted right-side pulse generator., Outcomes: The local inflammation and skin-picking behavior gradually improved. The stimulator device was re-implanted 4 months later., Lessons: We suggest that patients with the OC spectrum should be evaluated for skin-picking behaviors during presurgical and postsurgical follow-up to reduce the infection and device removal rates.

Background/aims: Rostral intralaminar thalamic nucleus (ILN) has been shown to modulate cognition through indirect connection with the hippocampus and prefrontal cortex. We explored the effects of deep brain stimulation (DBS) to the rostral ILN on spatial memory acquisition, brain neuronal activation and cortical and hippocampal synaptic changes in rats., Methods: The Morris water maze (MWM) task was used to evaluate the spatial memory of the rats. The expression of c-fos, an immediate early gene, was used to identify neural activation in the cerebral cortex and hippocampus. Synaptic changes in the somatosensory cortical and hippocampal neurons were explored with dendritic spine analysis following Golgi-Cox staining., Results: Our results showed that a barrage of DBS to the rostral ILN of normal rats significantly shortened their escape latency in MWM compared with sham-stimulated and untreated control rats. Rats with enhanced spatial memory had more c-fos immunoreactive cells in layer IV of the somatosensory cortex. Layer III cortical and CA1 hippocampal pyramidal neurons showed over 50% increase of dendritic spines, while only the proximal apical dendrites of layer V cortical pyramidal neurons had more dendritic spines., Conclusions: Rostral ILN-DBS activated neurons in the cerebral cortex and triggered cortical and hippocampal structural plasticity in association with spatial memory enhancement., (© 2016 S. Karger AG, Basel.)

Object: Deep brain stimulation (DBS) surgery under general anesthesia is an alternative option for patients with Parkinson's disease (PD). However, few studies are available that report whether neuronal firing can be accurately recorded during this condition. In this study the authors attempted to characterize the neuronal activity of the subthalamic nucleus (STN) and elucidate the influence of general anesthetics on neurons during DBS surgery in patients with PD. The benefit of median nerve stimulation (MNS) for localization of the dorsolateral subterritory of the STN, which is involved in sensorimotor function, was explored., Methods: Eight patients with PD were anesthetized with desflurane and underwent contralateral MNS at the wrist during microelectrode recording of the STN. The authors analyzed the spiking patterns and power spectral density (PSD) of the background activity along each penetration track and determined the spatial correlation to the target location, estimated mated using standard neurophysiological procedures., Results: The dorsolateral STN spiking pattern showed a more prominent bursting pattern without MNS and more oscillation with MNS. In terms of the neural oscillation of the background activity, beta-band oscillation dominated within the sensorimotor STN and showed significantly more PSD during MNS (p < 0.05)., Conclusions: Neuronal firing within the STN could be accurately identified and differentiated when patients with PD received general anesthetics. Median nerve stimulation can enhance the neural activity in beta-band oscillations, which can be used as an index to ensure optimal electrode placement via successfully tracked dorsolateral STN topography.

Background/purpose: Subthalamic nucleus deep brain stimulation (STN-DBS) has been shown to produce long-term symptom improvement in Parkinson's disease. The aim of this study was to identify the target symptoms that show the most improvement at 1 year and at 5 years after STN-DBS., Methods: This was a 5-year cohort study of 41 consecutive patients treated with bilateral STN-DBS. Clinical evaluations were performed 1 month prior to surgery and 1 year and 5 years after surgery. The outcome measurements at 1 year and 5 years were the changes compared with the baseline in Unified Parkinson's Disease Rating Scale (UPDRS) parts I, II, III, and IV scores, the Hoehn and Yahr stage, and Schwab and England Activities of Daily Living (SEADL) scores in the conditions of off-medication/on-stimulation and off-medication/off-stimulation. Further analysis included changes in the levodopa equivalent daily dose., Results: When compared to the preoperative baseline off-medication condition, significant improvements were observed in the UPDRS parts I, II, III, and IV and SEADL (p < 0.001) scores in the off-medication/on-stimulation condition 1 year after STN-DBS. Five years after STN-DBS, improvements in UPDRS scores were observed only for parts II, III, and IV (p < 0.001). In the off-medication/off-stimulation condition, no significant improvement was observed. At 5 years, significant deteriorations were observed in scores for the UPDRS part III axial subitem (p = 0.005), UPDRS part I (p = 0.005), UPDRS part II (p < 0.001), and SEADL (p = 0.001)., Conclusion: The long-term effect of STN-DBS on motor function is promising, although the magnitude of its effectiveness varied over the 5-year period., (Copyright © 2013. Published by Elsevier B.V.)

Objective: Age of onset is considered a poor prognostic factor for subthalamic deep brain stimulation (STN-DBS) outcome in the case of Parkinson's disease (PD). The goal of current study is to identify the long-term impact of STN-DBS for young onset PD (YOPD) patients., Methods: 17 YOPD patients with a mean disease onset at 32.3 years were prospectively followed up at 1, 2, 5 and 7 years after STN-DBS. Unified Parkinson's disease rating scale (UPDRS) was evaluated in 4 combinations of Med/DBS on/off., Results: UPDRS part II-IV improved significantly 7 years after operation. While a slowly progressive worsening of levodopa response on part III, synergistic effect of medication and stimulation consistently improves motor disabilities. STN-DBS could remarkably reduce levodopa equivalent daily dose at 7 years. The morbidity rates were low. However, these patients seem to have more transient stimulation dyskinesia (47.1%) and dopamine dysregulation syndrome (11.8%) after surgery., Conclusions: STN-DBS remains effective to improve motor disabilities over 7 years for YOPD and is a safe procedure concerning cognitive outcome and morbidity. However, stimulation dyskinesia and dopamine dysregulation syndrome deserve attention for the causal relationship between DBS surgery and behavioral outcomes., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Aims: Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) is a promising alternative to ablative surgery in treatment of refractory obsessive-compulsive disorder (OCD). A pilot study was conducted to assess 15-month outcomes of DBS in patients with refractory OCD in Taiwan., Methods: Four adult patients with a 3-year or more history of refractory OCD (Yale-Brown Obsessive-Compulsive Scale [Y-BOCS] score of at least 28) met the criteria for DBS surgery. DBS electrodes were implanted bilaterally in the VC/VS. Stimulation was adjusted for therapeutic benefit and absence of adverse effects. Psychiatric evaluation was conducted preoperatively, postoperatively, and at follow up at every 3 months for 15 months. Primary outcome measure was Y-BOCS. Secondary outcomes included the Hamilton Depression Rating Scale (HAM-D), and the Global Assessment of Function Scale., Results: Mean severity of OCD was a Y-BOCS score of 36.3 ± 2.1. At the end of 15 months' follow up, there was a 33.06% decrease in OCD severity (P = 0.001). Similar findings were seen for HAM-D (32.51% reduction, P = 0.005), and Global Assessment of Function Scale (31.03% increase, P = 0.026). In terms of adverse effects, two patients suffered from hypomania episodes after several weeks of DBS stimulation, and one had transient hypomania-like syndrome during DBS initial programming. One patient (Case 1) had an allergic reaction to implantation of the pulse generator in the chest, and another patient (Case 3) exhibited vertigo., Conclusions: We confirm that DBS of the VC/VS appears to be beneficial for improvements in function and mood among patients with treatment-resistant OCD. Compared to previous studies examining the therapeutic effects of DBS, no serious adverse effects were observed., (© 2012 The Authors. Psychiatry and Clinical Neurosciences © 2012 Japanese Society of Psychiatry and Neurology.)

Background: The efficacy and feasibility of bilateral subthalamic deep brain stimulation (STN-DBS) for Parkinson's disease (PD) under general anesthesia (GA) has not been evaluated., Objective: We compared the outcome of patients under GA with those who were operated on under local anesthesia (LA)., Material and Methods: Thirty-three patients were assigned to the GA group (desflurane) and 19 patients were assigned to the LA group. Microelectrode recording (MER) was performed in both groups. The surgical outcomes of the patients were evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) after at least 12 months after surgery., Results: Postoperatively, there was no significant difference on the UPDRS scores in either groups. A significant deterioration in cognitive function in the GA group was observed (p = 0.017). The recorded electrode coordinates, the average tracts for the MER, and STN depth were comparable in both groups. The overall incidence of adverse effects did not show any difference except that the incidence of sialorrhea and dysarthria was significantly higher in the GA group., Conclusion: Desflurane GA was shown to be a good alternative anesthetic method for PD patients undergoing DBS. Although the motor outcomes were comparable, a significant cognitive decline may be seen in the GA group with a higher occurrence of stimulation side effects., (Copyright © 2011 S. Karger AG, Basel.)

Background: The aim of this study is to determine whether stereotactic computed tomographic (CT) images fused with magnetic resonance images (MRI) is superior to stereotactic MRI alone in accuracy for targeting the subthalamic nucleus (STN) in deep brain stimulation (DBS)., Methods: During 2006 to 2007, 21 consecutive patients with Parkinson's disease were enrolled in this retrospective cohort study. CT Fusion group included 10 patients who underwent 20 procedures of STN-DBS under MRI-directed targeting in which the MRIs were fused to stereotactic CT images for surgical coordinates. MRI group included 11 patients who underwent 20 procedures under MRI-directed targeting alone., Results: After DBS surgery, in comparison to baseline levodopa (L-dopa) OFF, Unified Parkinson Disease Rating Scale, Part III scores improved by 43.6% ± 20.3% and 39.0% ± 15.6% (P = 0.60) in CT Fusion group and MRI group, respectively (L-dopa OFF/DBS ON). The mean decrease in L-dopa equivalent daily dose was 38.9% ± 26.3% and 36.7% ± 30.5% (P = 0.87), respectively. Single microelectrode recording (MER) trajectory procedure was experienced in 65% of patients in the CT Fusion group (13/20) and 45% of patients in the MRI group (9/20). The mean recorded STN length from initial to final MER trajectory in the CT Fusion and MRI groups was 4.3 mm (standard deviation [SD] = 1.8 mm)/5.1 mm (SD = 0.5 mm) and 3.6 mm (SD = 1.7 mm) (P = 0.214)/4.5 mm (SD = 0.7 mm) (P = 0.006), respectively. The final recorded STN length was significantly longer in the CT Fusion group., Conclusions: In-frame-based stereotactic STN targeting, an image fusion technique between stereotactic CT and MRI, can record a significantly longer STN length through limited MER compared with MRI alone. Whether this could translate into better clinical outcome and less morbidity still need a large and randomized trial., (Copyright © 2011 Elsevier Inc. All rights reserved.)

This 28-year-old Chinese man was referred for deep brain stimulation (DBS) evaluation for an 8-year history of refractory obsessive-compulsive disorder. After the patient had signed an informed consent, the authors implanted DBS leads. Hypomania with hypersexuality was noted on stimulation at Contact 2 and became aggravated with a higher voltage (> or = 3 V) during chronic bilateral DBS. After the voltage was decreased to 1 V, the patient's hypomanic symptoms subsided and his libido returned to baseline.

Background/aims: Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) has been shown to have long-term benefits in Parkinson's disease (PD). Through analyzing different variables, this study identified prognostic factors for the short- and long-term effects of STN-DBS., Methods: Thirty-six PD patients underwent bilateral STN-DBS. Clinical evaluations were performed 1 month before and 3 months after surgery, with additional follow-up examinations for a mean of 31.3 months., Results: There was a trend for long-term STN-DBS-induced improvements in the Unified Parkinson's Disease Rating Scale (UPDRS) part II and part III measures to be greater in younger patients. Preoperative levodopa responsiveness only led to consistent UPDRS part III improvement from STN-DBS at 3 months, and this predictive value did not exist in the long term. The preoperative levodopa response of tremor and axial symptoms in motor disability predicted long-term DBS effect only. Preoperative cognitive function positively correlated with postoperative improvement from DBS in UPDRS part III during long-term follow-up only., Conclusions: The prognostic factors for STN-DBS benefit were different for short- and long-term follow-ups. Good prognostic factors for long-term STN-DBS for PD patients were good cognitive function and tremor dominance. Poor prognostic factors were related to older age and non-dopaminergic-responsive axial disability., (Copyright 2009 S. Karger AG, Basel.)

Object: The authors of this preliminary study investigated the outcome and feasibility of intraoperative microelectrode recording (MER) in patients with Parkinson disease (PD) undergoing deep brain stimulation of the subthalamic nucleus (STN) after anesthetic inhalation., Methods: The authors conducted a retrospective analysis of 10 patients with PD who received a desflurane anesthetic during bilateral STN electrode implantation. The MERs were obtained as an intraoperative guide for final electrode implantation and the data were analyzed offline. The functional target coordinates of the electrodes were compared preoperatively with estimated target coordinates., Results: Outcomes were evaluated using the Unified Parkinson's Disease Rating Scale 6 months after surgery. The mean improvement in total and motor Unified Parkinson's Disease Rating Scale scores was 54.27 +/- 17.96% and 48.85 +/- 16.97%, respectively. The mean STN neuronal firing rate was 29.7 +/- 14.6 Hz. Typical neuronal firing patterns of the STN and substantia pars nigra reticulata were observed in each patient during surgery. Comparing the functional target coordinates, the z axis coordinates were noted to be significantly different between the pre- and postoperative coordinates., Conclusions: The authors found that MER can be adequately performed while the patient receives a desflurane anesthetic, and the results can serve as a guide for STN electrode implantation. This may be a good alternative surgical method in patients with PD who are unable to tolerate deep brain stimulation surgery with local anesthesia.

Objective: The neuropsychological effects of chronic subthalamic nucleus (STN)-deep brain stimulation (DBS) as a treatment for Parkinson's disease are variable. Whether these side effects result from the target per se or current diffusion into neighboring structures is uncertain. In this study, the relationship between clinical outcomes and coordinates of active contact are analyzed and compared between patients with and without neuropsychological sequelae., Methods: Thirty-eight Parkinsonian patients who underwent bilateral STN-DBS were enrolled in this retrospective cohort study. They were followed for at least 12 months. During the follow-up period, they were divided into two groups for comparison; Group A included patients with neuropsychological side effects and Group B was composed of patients without neuropsychological side effects. The position of the active contact of the electrode was defined with postoperative magnetic resonance imaging scans according to the midcommissural line. Active contact coordinates and clinical outcomes were compared for the two groups., Results: Among the 38 Parkinsonian patients who underwent STN-DBS, eight patients who had neuropsychological side effects were assigned to Group A; the other 30 patients were assigned to Group B. In Groups A and B, the mean follow-up periods were 13.9 and 12.1 months, respectively, the Unified Parkinson's Disease Rating Scale motor score was improved by 53.4 and 45.2% (P = 0.24), respectively, and the levodopa equivalent daily dosage was decreased by 68.4 and 46.4% (P = 0.16), respectively. The mean coordinates of active contact in both Groups A and B were x = 10.1 and 10.5 mm, respectively, y = -2.8 and -3.9 mm, respectively, and z = -6.3 and -6.2 mm, respectively, relative to the midcommissural point. A significant difference was observed on the y axis (P = 0.01)., Conclusion: When taking spatial influence into consideration, the neuropsychological effects of chronic STN-DBS were related to a significant anteriorly located active contact within the ventral STN in this preliminary study. This might suggest the existence of topography of STN in patients with Parkinson's disease concerning limbic and associative circuits.