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Objective: This experiment was conducted to evaluate the inclusion of dietary nontoxic sulfur (NTS) on growth performance, immune response, sulfur amino acid composition and meat characteristics in growing-finishing pigs.Methods: A total of 140 crossbred pigs ([Yorkshire×Landrace]×Duroc) with an average body weight of 34.73±0.66 kg were used for the 12-week feeding trial. Experimental pigs were allotted to one of 5 treatments in 4 replicates of 7 pigs per pen in a randomized complete block (RCB) design. The experimental treatments were as follows (0%, 0.1%, 0.2%, and 0.4% NTS levels): i) Control, corn soybean meal (SBM)-based diet; ii) NTS 0.1, basal diet + NTS 0.1%; iii) NTS 0.2, basal diet + NTS 0.2%; iv) NTS 0.4, basal diet + NTS 0.4%.Results: Body weight increased linearly as dietary NTS levels increased up to 0.2% (linear; p = 0.04) in the early finishing phase (9 weeks). During the whole experimental period, body weight and average daily gain linearly increased as the dietary NTS level increased in the diet (linear; both p = 0.01), but quadratic responses in body weight and average daily gain were observed with the addition of NTS 0.4% (quadratic, both p = 0.01). In the late finishing period, the IgG concentration increased linearly (linear; p = 0.01) as the dietary NTS level increased up to 4%. In the finishing period, a linear response was observed as a dietary NTS level was added (linear; p = 0.03), and supplementation with 0.2% NTS resulted in a higher methionine content than the other treatments (quadratic; p = 0.01). NST 0.2% had a lower value of thiobarbituric acid reactive substances (quadratic; p = 0.01).Conclusion: Consequently, supplementation with dietary NTS up to 0.2% could improve growth performance, amino acid composition in hair and meat antioxidation capacity.

Accreditation Council for Graduate Medical Education (ACGME)-accredited epilepsy fellowships, like other ACGME accredited training programs, use Milestones to establish learning objectives and to evaluate how well trainees are achieving these goals. The ACGME began developing the second iteration of the Milestones 6 years ago, and these are now being adapted to all specialties. Here, we describe the process by which Epilepsy Milestones 2.0 were developed and summarize them.A work group of nine board-certified, adult and pediatric epileptologists reviewed Epilepsy Milestones 1.0 and revised them using a modified Delphi approach.The new Milestones share structural changes with all other specialties, including a clearer stepwise progression in professional development and the harmonized Milestones that address competencies common to all medical fields. Much of the epilepsy-specific content remains the same, although a major addition is a set of Milestones focused on reading and interpreting electroencephalograms (EEGs), which the old Milestones lacked. Epilepsy Milestones 2.0 includes a Supplemental Guide to help program directors implement the new Milestones. Together, Epilepsy Milestones 2.0 and the Supplemental Guide recognize advances in epilepsy, including stereo-EEG, neurostimulation, genetics, and safety in epilepsy monitoring units.Epilepsy Milestones 2.0 address the shortcomings of the old Milestones and should facilitate the assessment of epilepsy fellowships and fellows by program directors, faculty, and fellows themselves.

Purpose Patients with respiratory failure associated with neurological dysfunction often require mechanical ventilator support, which poses increased economic burden and ventilator-associated complications. A diaphragm pacing system (DPS) is an implanted device that provides respiratory support for such patients. In this systematic review, we reviewed the literature to assess the safety and efficacy of DPS for patients with respiratory failure resulting from amyotrophic lateral sclerosis (ALS) or cervical spinal cord injuries. Materials and methods The following databases were searched from July 10 to July 30, 2018: MEDLINE, EMBASE, Cochran library, KoreaMed, Research Information Sharing Service, Korean studies Information Service System, Korea Institute of Science and Technology Information, and Korean Medical database. The abstracts and full texts of the searched articles were reviewed by two reviewers. Results The search keywords generated 197 articles: two randomized controlled trials, two case-control studies, and one case report involving patients with ALS; one cohort study, one case-control study, and two case reports involving patients with cervical spine injury; and one case report involving patients with both conditions were included. The primary outcome was safety profile (complications and adverse event) and efficacy (overall survival and sleep improvement). Complications and adverse events were more common in patients with ALS and spinal cord injury receiving DPS than in controls. Efficacy outcomes were inconsistent across ALS studies. Conclusion Based on safety and efficacy results, we do not support using DPS to manage respiratory failure in patients with ALS or cervical spine injury.

Spinocerebellar ataxia type-2 (SCA2) is an autosomal dominant cerebellar ataxia that occurs due to expanded CAG trinucleotide repeats in the ATXN2 gene. Clinical features of parkinsonism in SCA2 vary from phenotypes of levodopa-responsive parkinsonism to multiple system atrophy. We described a patient with SCA2 presenting typical clinical manifestations of multiple system atrophy-c type with levodopa responsive parkinsonism whose dopamine transporter (DAT) image showed atypically reduced DAT uptake in in the striatum.

Objective To examine interactions between cortical areas and between cortical areas and muscles during sensory tricks in cervical dystonia (CD). Methods Thirteen CD patients and thirteen age-matched healthy controls performed forewarned reaction time tasks, sensory tricks, and two tasks replicating aspects of the tricks (moving necks/arms). Control subjects mimicked sensory tricks. Corticocortical and corticomuscular coherence values were calculated from surface electrodes placed over motor, premotor, and sensory cortical areas and dystonic muscles. Results During initial preparation (after the warning stimulus), the only between-task difference was found in the γ-band corticocortical coherence (higher during tricks than during voluntary neck movements). With movements (before/after the imperative stimulus), the γ-band coherence of CD patients significantly increased during tricks but decreased during voluntary movements, while opposite trends were observed in healthy subjects. Additionally, the α- and β-band coherence decreased in healthy subjects during movements. Between the two patient subgroups (typical vs. forcible tricks), only those with typical tricks showed significant decrease in corticomuscular coherence during tricks. Conclusions Observed changes in the corticocortical coherence suggest that sensory tricks improve cortical function, which reduces corticomuscular connectivity and the dystonia. Significance We demonstrated that sensory tricks fundamentally affect sensorimotor integration in CD, both in movement preparation and execution.

Introduction The possibility of repetitive transcranial magnetic stimulation (rTMS) as an alternative therapy for essential tremor (ET) patients has emerged. However, its effect on medicated ET patients is lacking. The aim of this pilot study was to investigate the effect of cerebellar low-frequency rTMS as an “add-on” treatment. Methods In this single-blinded, randomized, sham-controlled pilot study, patients with ET were randomized into two groups, one receiving real-rTMS and the other sham-rTMS. For 5 days, 1200 stimulations per day were applied to the bilateral cerebellar hemispheres at an intensity of 90% of the resting motor threshold (RMT) with a frequency of 1-Hz. Motor evoked potentials (MEPs) and the Fahn-Tolosa-Marin tremor rating scales (TRS) were measured before, immediately, and 4 weeks after the completion of the rTMS procedures. All patients continued taking medications during all procedures. Results Among 22 patients, 12 and 10 patients were randomized into the real- and sham-rTMS groups, respectively. Repeated analysis of variance (ANOVA) measurements showed that the total TRS, TRS-A and B were changed both in real and sham-rTMS groups without interaction between time and group. TRS-C and MEPs, were not significantly changed at each follow-up point in either the real or sham-rTMS sessions. Conclusion We conclude that cerebellar low-frequency rTMS is safe, but has no significant effect as an “add-on” therapy in patients with ET.

The neural substrates of working memory are spread across prefrontal, parietal and cingulate cortices and are thought to be coordinated through low frequency cortical oscillations in the theta (3 – 8 Hz) and alpha (8 – 12 Hz) frequency bands. While the functional role of many subregions have been elucidated using neuroimaging studies, the role of superior frontal gyrus (SFG) is not yet clear. Here, we combined electrocorticography and direct cortical stimulation in three patients implanted with subdural electrodes to assess if superior frontal gyrus is indeed involved in working memory. We found left SFG exhibited task-related modulation of oscillations in the theta and alpha frequency bands specifically during the encoding epoch. Stimulation at the frequency matched to the endogenous oscillations resulted in reduced reaction times in all three participants. Our results support the causal role of SFG in working memory and suggest that SFG may coordinate working memory through low-frequency oscillations thus bolstering the feasibility of targeting oscillations for restoring cognitive function.

Background: The Multimer Detection System-Oligomeric amyloid-β (MDS-OAβ) level is a valuable blood-based biomarker for Alzheimer’s disease (AD). We used machine learning algorithms trained using multi-center datasets to examine whether blood MDS-OAβ values can predict AD-associated changes in the brain.Methods: A logistic regression model using TensorFlow (ver. 2.3.0) was applied to data obtained from 163 participants (amyloid positron emission tomography [PET]-positive and -negative findings in 102 and 61 participants, respectively). Algorithms with various combinations of features (MDS-OAβ levels, age, gender, and anticoagulant type) were tested 50 times on each dataset. Results: The predictive accuracy, sensitivity, and specificity values of blood MDS-OAβ levels for amyloid PET positivity were 78.16±4.97%, 83.87±9.40%, and 70.00±13.13%, respectively.Conclusions: The findings from this multi-center machine learning-based study suggest that MDS-OAβ values may be used to predict amyloid PET-positivity.

Additional file 1: Supplementary Table. The codes for prediction of the cognitive impairment with the two drawing test.

Background The Clock Drawing Test (CDT) and Rey–Osterrieth Complex Figure Test (RCFT) are widely used as a part of neuropsychological test batteries to assess cognitive function. Our objective was to confirm the prediction accuracies of the RCFT-copy and CDT for cognitive impairment (CI) using convolutional neural network algorithms as a screening tool. Methods The CDT and RCFT-copy data were obtained from patients aged 60–80 years who had more than 6 years of education. In total, 747 CDT and 980 RCFT-copy figures were utilized. Convolutional neural network algorithms using TensorFlow (ver. 2.3.0) on the Colab cloud platform (www.colab.research.google.com) were used for preprocessing and modeling. We measured the prediction accuracy of each drawing test 10 times using this dataset with the following classes: normal cognition (NC) vs. mildly impaired cognition (MI), NC vs. severely impaired cognition (SI), and NC vs. CI (MI + SI). Results The accuracy of the CDT was better for differentiating MI (CDT, 78.04 ± 2.75; RCFT-copy, not being trained) and SI from NC (CDT, 91.45 ± 0.83; RCFT-copy, 90.27 ± 1.52); however, the RCFT-copy was better at predicting CI (CDT, 77.37 ± 1.77; RCFT, 83.52 ± 1.41). The accuracy for a 3-way classification (NC vs. MI vs. SI) was approximately 71% for both tests; no significant difference was found between them. Conclusions The two drawing tests showed good performance for predicting severe impairment of cognition; however, a drawing test alone is not enough to predict overall CI. There are some limitations to our study: the sample size was small, all the participants did not perform both the CDT and RCFT-copy, and only the copy condition of the RCFT was used. Algorithms involving memory performance and longitudinal changes are worth future exploration. These results may contribute to improved home-based healthcare delivery.

Highlights • SEEG is feasible with little to no skull to anchor a bolt. • To the best of our knowledge, this is the first report describing SEEG electrode placement with no skull bone., Stereo electroencephalogram (SEEG) electrode placement with cranially fixed guide bolts is recognized as one of the most accurate and safest implantation strategies to sample deep and buried cortex during certain clinical scenarios involving epilepsy surgery. Bone thickness of less than 2 mm is a relative contraindication to SEEG. Here, we describe a case drug-resistant focal epilepsy where prior craniotomies, infections and radiation therapy yielded limited skull bone requiring invasive EEG monitoring. Due to the inability to use bolts over areas with limited skull bone, we successfully utilized a combination of the standard and a modified SEEG techniques for implantation and stabilization of intracranial electrodes without complications. This strategy enabled optimal intracranial EEG monitoring and surgical management of the patient’s drug-resistant focal seizures.

Background: While idiopathic focal dystonia (IFD) and essential tremor (ET) have been considered pure movement disorders, they reportedly induce neuropsychiatric manifestations and may thus be more accurately described as network disorders. Methods: The present multi-center, cross-sectional, case-control study evaluated the severity of depression and anxiety with the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI), respectively; the frequency of neuropsychiatric disorders with the Korean-Mini International Neuropsychiatry Interview; and QoL with the Short-Form 36 (SF-36). Results: Seventy-four subjects participated in this study (IFD, 27; ET, 24; controls, 23). The BDI and BAI scores were higher in the IFD and ET groups than in the control group. Although the frequency of neuropsychiatric disorders diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Axis I was comparable among the groups, the prevalence of major depressive disorder tended to be high among patients with IFD. QoL was correlated with the severity of depression and anxiety across the groups. Conclusions: Depression and anxiety are more severe in patients with IFD and ET compared to healthy controls, while their severity is similar among patients with IFD and ET. Axis I major depressive disorder is relatively more prevalent in patients with IFD. Neuropsychiatric symptoms affect QoL regardless of the affected individual's condition, addressing neuropsychiatric symptoms in patients with movement disorders may be crucial to improving their QoL.

Introduction Although sensory tricks are well known as the maneuvers that temporarily relieve dystonic symptoms in patients with cervical dystonia (CD), the underlying neurophysiological mechanisms remain unclear. We aimed to investigate brain potentials related to sensory tricks in patients with CD. Methods Thirteen patients with CD and 13 age-matched healthy volunteers participated. The experiment consisted of three conditions (moving the neck, moving an arm, and performing sensory tricks) presented in different blocks in random order in a contingent negative variation (CNV) paradigm. Warning and trigger stimuli (S1 and S2) were presented to the participants, who were instructed to prepare to perform the specific task for each condition after S1, and then to perform the task after S2. Early and late components of the CNV were measured. Results The late CNVs in patients with CD were significantly larger than those in healthy participants in Fz, FCz, Cz, and C3 electrodes. Only in patients with CD, the late CNVs were significantly greater for the ‘sensory tricks’ condition compared to the ‘move neck’ condition in Fz and C3 electrodes. Conclusion The late CNV is increased during sensory tricks in patients with CD, suggesting that sensory tricks may affect mechanisms related to the motor preparatory phase in the premotor and primary motor areas. Sensory tricks may normalize impaired motor preparation in dystonia, leading to improved dystonic symptoms.

Purpose The aim of this study was to investigate the association between autonomic dysfunction and striatal dopamine depletion or metabolic changes in de novo Parkinson disease (PD). Methods Based on the Composite Autonomic Severity Score (CASS), patients with de novo PD were classified into PD with (PD-AUT+) and without autonomic dysfunction (PD-AUT-) groups. We compared the dopamine transporter (DAT) availability in the striatum by quantitatively measuring F-FP-CIT PET between both groups. We also assessed the association between DAT availability and the CASS. In addition, we compared regional uptake in early-phase images of F-FP-CIT PET as well as cortical thickness between the PD-AUT+ and PD-AUT- groups. Results The PD-AUT+ group had significantly lower DAT availability in all striatal subregions than did the PD-AUT- group. The total CASS was significantly correlated with DAT availability in all striatal subregions. In addition, the subscores of the adrenergic component were correlated with DAT availability in all striatal subregions. The subscores of the cardiovagal component were negatively correlated with DAT availability in the caudate and ventral striatum. In early-phase F-FP-CIT PET, the PD-AUT+ group exhibited decreased regional perfusion in the parieto-occipital areas and increased regional perfusion in the pallidothalamic, pontocerebellar, inferior frontal, and primary motor areas compared with the PD-AUT- group. There were no regions of different cortical thickness between the PD groups. Conclusions The present study revealed that autonomic dysfunction is closely linked to striatal dopamine depletion and prominent PD-related perfusion patterns in de novo PD, suggesting a greater pathological burden in patients with dysautonomia.

Parkinsonism is a clinical syndrome presenting with bradykinesia, tremor, rigidity, and postural instability. Nonmotor symptoms have recently been included in the parkinsonian syndrome, which was traditionally associated with motor symptoms only. Various pathologically distinct and unrelated diseases have the same clinical manifestations as parkinsonism or parkinsonian syndrome. The etiologies of parkinsonism are classified as neurodegenerative diseases related to the accumulation of toxic protein molecules or diseases that are not neurodegenerative. The former class includes Parkinson's disease (PD), multiple-system atrophy, progressive supranuclear palsy, and corticobasal degeneration. Over the past decade, clinical diagnostic criteria have been validated and updated to improve the accuracy of diagnosing these diseases. The latter class of disorders unrelated to neurodegenerative diseases are classified as secondary parkinsonism, and include drug-induced parkinsonism (DIP), vascular parkinsonism, and idiopathic normal-pressure hydrocephalus (iNPH). DIP and iNPH are regarded as reversible and treatable forms of parkinsonism. However, studies have suggested that the absence of protein accumulation in the nervous system as well as managing the underlying causes do not guarantee recovery. Here we review the differential diagnosis of PD and parkinsonism, mainly focusing on the clinical aspects. In addition, we describe recent updates to the clinical criteria of various disorders sharing clinical symptoms with parkinsonism.

Purpose Epilepsy surgery is the most successful method of treating medically unresponsive epilepsy, but carries a risk of morbidity. PET/MR is an emerging technique that increases detection of focal lesions whose resection may result in symptom remission. Methods Retrospective review of 74 focal epilepsy patients over a period of 3 years who had a PET/MR was performed following IRB permission and informed consent. 27 patients underwent surgery or RNS (responsive neurostimulator) placement. Results Hybrid PET-MR identified new anatomic or functional lesions in 10 patients not identified with standalone 3 T MR. Of the 27 patients who underwent focal surgery (19) or RNS placement (8), 24 showed improvement (Engel’s I-III), 2 did not (Engel’s IV), and one had an RNS explanted due to infection. MR and PET were read by 2 separate neuroradiologists and nuclear medicine physicians, respectively. Modalities were evaluated in terms of ability to detect the correct lobe and side for a focal lesion whose resection improved symptoms. Prior standalone MR exhibited 71–77% sensitivity and 0% specificity (as there were only 2 nonresponders), MR associated with PET/MR had 68–71% sensitivity and 0–50% specificity (depending on whether a lesion was seen on one of the nonresponders), and PET had 68–71% sensitivity and 25–33% specificity. Using either PET or MR to identify a focal lesion, PET/MR had sensitivity of 78–82% and specificity 0–50%. Conclusions PET-MR provides additional sensitivity when used as two combined modalities for detecting possible epileptic foci.

Choline alphoscerate in clinical studies improved cognitive dysfunction in dementia, but it did not show any clear clinical benefit on mild cognitive impairment (MCI). There is limited evidence of neuropsychological markers in showing the effects of cholinergic precursors in MCI. Object of this preliminary study is to evaluate the change of the P300 latency as a biomarker for cognitive function after taking choline alphoscerate in patients with MCI. Event related evoked potential study were done in baseline (n = 27) and 3 months after taking choline alphoscerate (n = 17). When compared to our previous reported control database, the difference of the P300 latencies between MCI and control group at baseline was statistically significant (P

Inert biomaterials used for auricular reconstruction, which is one of the most challenging and diverse tasks in craniofacial or head and neck surgery, often cause problems such as capsule formation, infection, and skin extrusion. To solve these problems, scaffold consisting of inert biomaterial, high-density polyethylene (Medpor®) encapsulated with neocartilage, biodegradable poly(DL-lactic-co-glycolic acid) (PLGA) was created using a tissue engineering strategy. PLGA scaffold without Medpor® was created to serve as the control. Scaffolds were vacuum-seeded with rabbit chondrocytes, freshly isolated from the ear by enzymatic digestion. Then, cell-seeded scaffolds were implanted subcutaneously in the dorsal pockets of nude mice. After 12 weeks, explants were analyzed by histological, biochemical, and mechanical evaluations. Although the PLGA group resulted in neocartilage formation, the PLGA–Medpor® group demonstrated improved outcome with the formation of well-surrounded cartilage around the implants with higher mechanical strength than the PLGA group, indicating that Medpor® has an influence on the structural strength of engineered cartilage. The presence of collagen and elastin fibers was evident in the histological section in both groups. These results demonstrated a novel method of coating implant material with engineered cartilage to overcome the limitations of using biodegradable scaffold in cartilage tissue regeneration. By utilizing the patient’s own chondrocytes, our proposed method may broaden the choice of implant materials while minimizing side effects and immune reaction for the future medical application.

Author(s): Hirsch, Lawrence J; Mirro, Emily A; Salanova, Vicenta; Witt, Thomas C; Drees, Cornelia N; Brown, Mesha-Gay; Lee, Ricky W; Sadler, Toni L; Felton, Elizabeth A; Rutecki, Paul; Shin, Hae Won; Hadar, Eldad; Hegde, Manu; Rao, Vikram R; Mnatsakanyan, Lilit; Madhavan, Deepak S; Zakaria, Tarek J; Liu, Anli A; Heck, Christianne N; Greenwood, Janet E; Bigelow, Jeffrey K; Nair, Dileep R; Alexopoulos, Andreas V; Mackow, Michael; Edwards, Jonathan C; Sotudeh, Nadia; Kuzniecky, Ruben I; Gwinn, Ryder P; Doherty, Michael J; Geller, Eric B; Morrell, Martha J | Abstract: ObjectiveTo describe seizure outcomes in patients with medically refractory epilepsy who had evidence of bilateral mesial temporal lobe (MTL) seizure onsets and underwent MTL resection based on chronic ambulatory intracranial EEG (ICEEG) data from a direct brain-responsive neurostimulatorn(RNS) system.MethodsWe retrospectively identified all patients at 17 epilepsy centers with MTL epilepsy who were treated with the RNS System using bilateral MTL leads, and in whom an MTL resection was subsequently performed. Presumed lateralization based on routine presurgical approaches was compared to lateralization determined by RNS System chronic ambulatory ICEEG recordings. The primary outcome was frequency of disabling seizures at last 3-month follow-up after MTL resection compared to seizure frequency 3nmonths before MTL resection.ResultsWe identified 157 patients treated with the RNS System with bilateral MTL leads due to presumed bitemporal epilepsy. Twenty-five patients (16%) subsequently had an MTL resection informed by chronic ambulatory ICEEG (meann=n42nmonths ICEEG); follow-up was available for 24 patients. After MTL resection, the median reduction in disabling seizures at last follow-up was 100% (mean: 94%; range: 50%-100%). Nine patients (38%) had exclusively unilateral electrographic seizures recorded by chronic ambulatory ICEEG and all were seizure-free at last follow-up after MTL resection; eight of nine continued RNS System treatment. Fifteen patients (62%) had bilateral MTL electrographic seizures, had an MTL resection on the more active side, continued RNS System treatment, and achieved a median clinical seizure reduction of 100% (mean: 90%; range: 50%-100%) at last follow-up, with eight of fifteen seizure-free. For those with more than 1nyear of follow-up (Nn=n21), 15 patients (71%) were seizure-free during the most recent year, including all eight patients with unilateral onsets and 7 of 13 patients (54%) with bilateral onsets.SignificanceChronic ambulatory ICEEG data provide information about lateralization of MTL seizures and can identify additional patients who may benefit from MTL resection.

Glutamic acid decarboxylase 65‐kilodalton isoform (GAD65) antibodies have been associated with multiple nonneurological and neurological syndromes including autoimmune epilepsy (AE). Although immunotherapy remains the cornerstone for the treatment of AE, those with GAD65 Ab‐associated AE (GAD65‐AE) remain refractory to immunotherapy and antiseizure medication (ASM). Outcomes of epilepsy surgery in this patient population have also been unsatisfactory. The role of neuromodulation therapy, particularly direct brain‐responsive neurostimulation therapy, has not been previously examined in GAD65‐AE. Here, we describe four consecutive patients with refractory GAD‐65‐associated temporal lobe epilepsy (GAD65‐TLE) receiving bilateral hippocampal RNS System treatment. The RNS System treatment was well tolerated and effective in this study cohort. Three patients had a >50% clinical seizure reduction, and one patient became clinically seizure‐free following resective surgery informed by the RNS System data with continued RNS System treatment. In all four of our patients, the long‐term ambulatory data provided by the RNS System allowed us to gain objective insights on electrographic seizure lateralization, patterns, and burden as well as guided immunotherapy and ASM optimization. Our results suggest the potential utility of the RNS System in the management of ASM intractable GAD65‐AE.

Background Parkinson’s disease (PD) and drug-induced parkinsonism (DIP) are the major diseases of parkinsonism. To better understand parkinsonism, we aimed to assess the prevalence and incidence of PD and DIP in Korea from 2012 to 2015. Methods We used the Health Insurance Review and Assessment Service database, which covers the entire population in Korea. We used claims during 2011–2015 to assess epidemiology of PD and DIP during 2012–2015. Retrospective cross-sectional study design was employed to assess prevalence, whereas retrospective cohort study design was used to determine incidence. Patients with at least one claim with ICD-10 G20 and who received antiparkinsonian drugs for at least 60 days were classified as having PD. We excluded patients with antiparkinsonian drugs that can be used for indications other than PD. Patients with at least one claim with ICD-10 G211 or G251 during the prescription period of drugs that are frequently related with DIP were classified as having DIP. Incident cases had a disease-free period of 1 year before diagnosis. To evaluate the significance of changes in the prevalence or incidence over time, Poisson regression was used to determine p for trend. Results The prevalence of PD increased from 156.9 per 100,000 persons in 2012 to 181.3 per 100,000 persons in 2015 (p for trendp for trendp for trendp for trend Conclusions Our study suggests that the incidence of PD has gradually decreased whereas, the incidence of DIP increased from 2012 to 2015. Further studies are warranted to examine possible causes of increased DIP incidence in order to develop management strategy for parkinsonism.

The cerebellum has recently been highlighted as a key neural substrate responsible for dystonia. A 57-year-old female presented with isolated focal leg dystonia that developed 8 years after acute cerebellar infarction. Brain magnetic resonance imaging showed an old cerebellar infarct in the right anterior cerebellum. Low-frequency cerebellar repetitive transcranial magnetic stimulation on the right cerebellum partially improved dystonia in this patient. This case provides valuable evidence on cerebellar mechanisms related to the development of dystonia in a topographically specific manner. Cerebellar brain stimulation can be a potential therapeutic strategy for patients with dystonia.

Summary: Working memory is mediated by the coordinated activation of frontal and parietal cortices occurring in the theta and alpha frequency ranges. Here, we test whether electrically stimulating frontal and parietal regions at the frequency of interaction is effective in modulating working memory. We identify working memory nodes that are functionally connected in theta and alpha frequency bands and intracranially stimulate both nodes simultaneously in participants performing working memory tasks. We find that in-phase stimulation results in improvements in performance compared to sham stimulation. In addition, in-phase stimulation results in decreased phase lag between regions within working memory network, while anti-phase stimulation results in increased phase lag, suggesting that shorter phase lag in oscillatory connectivity may lead to better performance. The results support the idea that phase lag may play a key role in information transmission across brain regions. Thus, brain stimulation strategies to improve cognition may require targeting multiple nodes of brain networks. : Alagapan et al. use intracranial stimulation to simultaneously target multiple nodes of the working memory network. Functional connectivity within the network increases with stimulation, while task performance and phase lag between nodes in the network depend on the relative timing between stimulation. Keywords: cortical oscillations, intracranial eeg, human neuroscience, direct cortical stimulation, brain stimulation, working memory, phase lag

Additional file 3: Figure S2. Sensitivity analysis. Number of incident patients with drug-induced parkinsonism by the types and numbers of offending drugs in Korea

Additional file 1: Table S1. Medications specifically used for Parkinson’s disease. Table S2. Frequencies and prevalence of Parkinson’s disease in Korea from 2012 to 2015. Table S3. Frequencies and prevalence of drug-induced parkinsonism in Korea from 2012 to 2015. Table S4. Frequencies and incidence of Parkinson’s disease in Korea from 2012 to 2015. Table S5. Frequencies and incidence of drug-induced parkinsonism in Korea from 2012 to 2015.