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Abstract Dual cognitive-walking treadmill training (DTT), designed to replicate real-life walking conditions, has shown promise effect in individuals with Parkinson’s disease (PD). This study aims to compare the effects of DTT versus single treadmill training (STT) on cognitive and walking performance under both single and dual task conditions, as well as on fall, patients’ subjective feeling, and quality of life. Sixteen individuals with PD were randomly assigned to DTT or STT group and underwent 8 weeks of training. The DTT group received treadmill training with cognitive loads, while the STT group received treadmill training without cognitive load. Outcome measures included gait parameters (speed, step length) and cognitive performance (reaction time, accuracy, composite score) under both single and dual task conditions. Unified Parkinson’s Disease Rating Scale-part III (UPDRS-III), Falls Efficacy Scale (FES), Patient Global Impression of Change (PGIC), and Parkinson’s Disease Questionnaire (PDQ-39) were also measured. Both DTT and STT groups showed increased comfortable walking speed and step length. Only the DTT group demonstrated significant improvements in cognitive composite score under both single and dual task conditions, as well as UPDRS-III, FES, and PDQ-39(p

Abstract Background Non-invasive techniques such as central intermittent theta burst stimulation (iTBS) and repetitive peripheral magnetic stimulation (rPMS) have shown promise in improving motor function for patients with stroke. However, the combined efficacy of rPMS and central iTBS has not been extensively studied. This randomized controlled trial aimed to investigate the synergistic effects of rPMS and central iTBS in patients with stroke. Method In this study, 28 stroke patients were randomly allocated to receive either 1200 pulses of real or sham rPMS on the radial nerve of the affected limb, followed by 1200 pulses of central iTBS on the ipsilesional hemisphere. The patients received the intervention for 10 sessions over two weeks. The primary outcome measures were the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) and the Action Research Arm Test (ARAT). Secondary outcomes for activities and participation included the Functional Independence Measure-Selfcare (FIM-Selfcare) and the Stroke Impact Scale (SIS). The outcome measures were assessed before and after the intervention. Results Both groups showed significant improvement in FMA-UE and FIM-Selfcare after the intervention (p

In this paper, we propose a data-shifting neural network (DSNN) for the detection of abnormal heartbeats. Our study aims to identify six types of electrocardiogram (ECG) signals using the deep learning network. In order to enhance the detection accuracy, the DSNN is devised by doubling the input signal using a data shifting scheme so that the amount of information for training may be adequately sufficient. Although the computational time doubles, the accuracy can be improved. When implemented using the Taiwan Semiconductor Manufacturing Company (TSMC) $0.18-\mu m$ complementary metal oxide semiconductor (CMOS) process, the proposed DSNN chip has an operating frequency at 20 MHz with chip area of $0.619 mm^{2}$ and maximum power dissipation $0.75 mW$ . As a result, the proposed DSNN can substantially increase detection accuracy for the task of ECG heartbeat classification. Results obtained after applying the proposed circuit to the ECG signals drawn from the MIT-BIH arrhythmia database showed that it achieved a detection rate of 97.17% with a small chip area, suggesting that it may be suitable for wearable or portable devices in healthcare.

Gait disorders are a fundamental challenge in Parkinson’s disease (PD). The use of laser-light visual cues emitted from shoes has demonstrated effective in improving freezing of gait within less restrictive environments. However, the effectiveness of shoes-based laser-light cueing may vary among individuals with PD who have different types of impairments. We introduced an innovative laser-light visual shoes system capable of producing alternating visual cues for the left and right feet through one-side cueing at a time, while simultaneously recording foot inertial data and foot pressures. The effects of this visual cueing system on gait patterns were assessed in individuals with PD, both those with well-gait and those with worse-gait. Our device successfully quantified gait characteristics, including the asymmetry in the center of pressure trajectory, in individuals with PD. Furthermore, visual cueing prolonged stride times and increased the percentage of stance phase, while concurrently reducing stride length in PD individuals with well-gait. Conversely, in PD individuals with worse-gait, visual cueing resulted in a decreased freeze index and a reduction in the proportion of intervals prone to freezing episodes. The effects of visual cueing varied between PD individuals with well-gait and those with worse-gait. Visual cueing slowed down gait in the well-gait group while it appeared to mitigate freezing episodes in worse-gait group. Future researches, including enhancements to extend the projection distance of visual cues and clinical assessments conducted in real-world settings, will help establish the clinical utility of our proposed visual cueing system.

Background: Theta burst stimulation (TBS), a patterned repetitive transcranial magnetic stimulation (rTMS) protocol with shorter simulation duration and lower stimulus intensity, could be a better protocol for individuals with autism spectrum disorder (ASD). Our study aimed to explore the impacts of intermittent TBS (iTBS) over the bilateral posterior superior temporal sulcus (pSTS) on intellectually able adults with ASD. Methods: In this randomized, single-blinded, sham-controlled crossover trial, 13 adults with ASD completed iTBS for 5 consecutive days over the bilateral pSTS and inion (as a sham control) in a 16-weeks interval and in a randomly assigned order. The neuropsychological function was measured with the Wisconsin Card Sorting Test (WCST) for cognitive flexibility while the clinical outcomes were measured with both self-rate and parents-rate Autism Spectrum Quotient (AQ) before and after 5-day iTBS interventions. Results: The results revealed significantly immediate effects of multi-session iTBS over the bilateral pSTS on parent-rate autistic symptoms in adults with ASD. The post-hoc analysis revealed the impacts of multi-session iTBS on cognitive flexibility were affected by baseline social-communicative impairment and baseline cognitive performance. Besides, the impacts of multi-session iTBS on clinical symptoms was affected by the concurrent psychotropic medication use and baseline autistic symptoms. Conclusions: Given the caveat of the small sample size and discrepancy of multiple informants, this pilot study suggests the therapeutic potential of 5-day multi-session iTBS over the pSTS in adults with ASD. Individual factors modulating the response to rTMS should be explicitly considered in the future trial.

IntroductionREM Sleep Behavior Disorder (RBD) has been highlighted to identify a patient with prodromal Parkinson’s disease (PD). Although many studies focus on biomarkers to predict an RBD patient’s evolution from prodromal PD to clinical PD, the neurophysiological perturbation of cortical excitability has not yet been well elucidated. Moreover, no study describes the difference between RBD with and without abnormal TRODAT-1 SPECT.MethodsBy measuring the amplitude of motor evoked potentials (MEP), the cortical excitability changes after transcranial magnetic stimulation (TMS) were evaluated in 14 patients with RBD and eight healthy controls (HC). Seven of the 14 patients with RBD showed abnormal TRODAT-1 (TRA-RBD), and seven were normal (TRN-RBD). The tested parameters of cortical excitability include resting motor threshold (RMT), active motor threshold (AMT), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), contralateral silence period (CSP), and input–output recruitment curve.ResultsThe RMT and AMT showed no difference among the three studied groups. There was only SICI at inter-stimuli-interval 3 ms revealing group differences. The TRA-RBD demonstrated significant differences to HC in these aspects: decreased SICI, increased ICF, shortening of CSP, and augmented MEP amplitude at 100% RMT. Moreover, the TRA-RBD had a smaller MEP facilitation ratio at 50% and 100% of maximal voluntary contraction when compared to TRN-RBD. The TRN-RBD did not present any difference to HC.ConclusionWe showed that TRA-RBD shared similar cortical excitability changes with clinical PD. These findings would provide further insight into the concept that RBD is the highly prevalent entity in prodromal PD.

This paper presents a very large–scale integration chip for a novel discrete wavelet transform (DWT) based QRS complex detection algorithm. In many aspects of electrocardiogram (ECG) analyses, QRS complex detection is the first step. For example, heart rate variability (HRV) is evaluated based on the RR interval and thus, an accurate QRS detection algorithm would substantially affect the subsequent steps in HRV analysis. On the other hand, since wireless monitoring currently remains prohibitively expensive and lowering the cost and power consumption of wireless monitoring depends upon a reduction in the complexity of the algorithm, in this study we propose a simple, reliable, low power and cost-effective QRS detection method and its VLSI implementation. Here, the task of the QRS complex detection is performed using the quadratic spline wavelet transform based wavelet packet decomposition. After a four-level DWT decomposition, in order to enhance the QRS complex a novel noise level detection is then performed. The proposed noise level detector would select two of the four wavelet coefficients and then calculate their product. As a result, in addition to DWT, the processing stage includes the product of the two selected wavelet coefficients, adaptive thresholding scheme, and the execution of decision rules. Fabricated on an 0.18- $\mu \text{m}$ complementary metal oxide semiconductor, the 1-KHz processor draws only $4.2~\mu \text{W}$ of power, and the chip area is only $0.83~mm^{2}$ . Also, the detection accuracy of the proposed method is further verified using 48 recordings from the MIT-BIH arrhythmia database (Se = 99.57%, $+\text{P}\,\,= 99.59\%$ ), suggesting that the proposed QRS detector may achieve a high accuracy and cost-effective QRS complex detection.

Objective: To determine the impact of an operator’s experience on transcranial magnetic stimulation (TMS) measurement. Methods: Operator B (beginner), operator E (expert), and 30 healthy participants joined the study consisting of two experiments. In each experiment, each operator performed a TMS protocol on each participant in a random order. Results: Compared with operator E, operator B exhibited higher resting motor threshold (RMT) in experiment I (60.1 ± 13.0 vs. 57.4 ± 10.9% maximal stimulation output, p = 0.017) and the difference disappeared in experiment II (p = 0.816). In 1-mV motor evoked potential (MEP) measurement, operator B exhibited higher standard deviation indicating lower consistency in experiment I compared with experiment II (1.05 ± 0.40 vs. 1.05 ± 0.16 mV with unequal variances, p = 0.001) and had poor intrarater reliability between the experiments (intraclass correlation coefficient = −0.130). There was no difference in the results of active motor threshold, silent period, paired-pulse stimulation, or continuous theta burst stimulation between the operators. Conclusions: An operator’s experience in TMS may affect the results of RMT measurement. With practice, a beginner may choose a more precise stimulation location and have higher consistency in 1-mV MEP measurement. Significance: We recommend that a beginner needs to practice for precise stimulation locations before conducting a trial or clinical practice.

Following the published behavioral and cognitive results of this single-blind parallel sham-controlled randomized clinical trial, the current study aimed to explore the impact of intermittent theta burst stimulation (iTBS), a variant of excitatory transcranial magnetic stimulation, over the bilateral posterior superior temporal sulci (pSTS) on white matter macro/microstructure in intellectually able children and adolescents with autism. Participants were randomized and blindly received active or sham iTBS for 4 weeks (the single-blind sham-controlled phase). Then, all participants continued to receive active iTBS for another 4 weeks (the open-label phase). The clinical results were published elsewhere. Here, we present diffusion magnetic resonance imaging data on potential changes in white matter measures after iTBS. Twenty-two participants in Active-Active group and 27 participants in Sham-Active group underwent multi-shell high angular resolution diffusion imaging (64-direction for b = 2000 & 1000 s/mm2, respectively) at baseline, week 4, and week 8. With longitudinal fixel-based analysis, we found no white matter changes following iTBS from baseline to week 4 (a null treatment by time interaction and a null within-group paired comparison in the Active-Active group), nor from baseline to week 8 (null within-group paired comparisons in both Active-Active and Sham-Active groups). As for the brain-symptoms relationship, we did not find baseline white matter metrics associated with symptom changes at week 4 in either group. Our results raise the question of what the minimal cumulative stimulation dose required to induce the white matter plasticity is.

Abstract Nonmotor symptoms (NMSs) cause major burden in patients with Parkinson’s disease (PD). Previous NMSs progression studies mostly focused on the prevalence. We conducted a longitudinal study to identify the progression pattern by the severity. PD patients recruited from the outpatient clinics of a tertiary medical center were evaluated by the Unified Parkinson's Disease Rating Scale and Non-Motor Symptoms Scale (NMSS). A retrospective study with three-step analysis was performed. Step 1, the NMSs severity was compared among patients stratified by disease duration every 2 years up to 10 years. Step 2, patients with repeated tests in 2 years were categorized into 4 groups by the diseased duration of every 5 years. Step 3, the NMSS score changes in 6 years follow-up were determined, and the dosage of anti-PD drugs was compared to the NMSs severity changes. 676 patients completed the step 1 analysis, which showed a trend of NMSs worsening but not significant until the disease duration longer than 4–6 years. Furthermore, the severity did not change between repeated evaluations in 2 years in all patients. The progression became apparent after 6 years. Individual symptoms had different progression patterns and the increment of medications was independent to NMSs evolution. We demonstrated the NMSs severity progression in Taiwanese PD patients and the independence of the medications and NMSs progression.

Abstract Background Real-world impact of extended-release formulations of oral drugs should ideally be evaluated in population-based health data. Objective To evaluate changes in utilization of the dopamine agonist pramipexole for Parkinson’s disease after the introduction of extended-release (ER) pramipexole in Taiwan. Patients and Methods Source data were derived from National Health Insurance claims. Patients with a diagnosis of Parkinson’s disease and pramipexole prescriptions were identified. Drug use patterns from 2009 through 2011 (only the immediate-release [IR] formulation was available) and from 2012 through 2017 (both the IR and ER formulations were available) were assessed. Outcomes of interest were levodopa equivalent dose per day (LEDD) and 1-year adherence, as measured by the medication possession ratio (MPR). Results LEDDs associated with pramipexole ER prescriptions were more than twice as large as that associated with pramipexole IR, both in pramipexole used in monotherapy and that used in combination therapy. One-year MPRs for pramipexole ER initiators were all larger than 73% from 2012 through 2016 and 1-year MPRs for pramipexole IR initiators were less than 65% in 2010 and 2011. Conclusion Introduction of pramipexole ER to Taiwan resulted in higher LEDD in prescriptions with pramipexole. Patients with Parkinson’s disease who were initiated on pramipexole ER had better adherence to the medication than those who were prescribed pramipexole IR.

The strength of lower extremity is important for individuals to maintain balance and ambulation functions. The previous studies showed that individuals with Parkinson’s disease suffered from fatigue and strength loss of central origin. The purpose of this study was to investigate the effect of lower extremities’ cycling training on different components of force and fatigue in individuals with Parkinson’s disease. Twenty-four individuals (13 males, 11 females, mean age: 60.58 ± 8.21 years) diagnosed with idiopathic Parkinson’s disease were randomized into training and control groups. The maximum voluntary contraction (MVC) force, voluntary activation level (VA), and twitch force of knee extensors were measured using a custom-made system with surface electrical stimulation. The general, central, and peripheral fatigue indexes (GFI, CFI, and PFI) were calculated after a fatiguing cycling protocol. Subjects received 8 weeks of low resistance cycling training (training group) or self-stretching (control group) programs. Results showed that MVC, VA, and twitch force improved (p < 0.05) only in the training group. Compared to the baseline, central fatigue significantly improved in the training group, whereas peripheral fatigue showed no significant difference in two groups. The cycling training was beneficial for individuals with Parkinson’s disease not only in muscle strengthening but also in central fatigue alleviation. Further in-depth investigation is required to confirm the effect of training and its mechanism on central fatigue.

Fall detection and physical activity (PA) classification are important health maintenance issues for the elderly and people with mobility dysfunctions. The literature review showed that most studies concerning fall detection and PA classification addressed these issues individually, and many were based on inertial sensing from the trunk and upper extremities. While shoes are common footwear in daily off-bed activities, most of the aforementioned studies did not focus much on shoe-based measurements. In this paper, we propose a novel footwear approach to detect falls and classify various types of PAs based on a convolutional neural network and recurrent neural network hybrid. The footwear-based detections using deep-learning technology were demonstrated to be efficient based on the data collected from 32 participants, each performing simulated falls and various types of PAs: fall detection with inertial measures had a higher F1-score than detection using foot pressures; the detections of dynamic PAs (jump, jog, walks) had higher F1-scores while using inertial measures, whereas the detections of static PAs (sit, stand) had higher F1-scores while using foot pressures; the combination of foot pressures and inertial measures was most efficient in detecting fall, static, and dynamic PAs.

Background: To investigate the effect and dose-response of functional electrical stimulation cycling (FES-cycling) training on spasticity in the individuals with spinal cord injury (SCI).Method: Five electronic databases [PubMed, Scopus, Medline (Proquest), Embase, and Cochrane Central Register of Controlled Trials (CENTRAL)] were searched before September 2021. The human trials and studies of English language were only included. Two authors independently reviewed and extracted the searched studies. The primary outcome measure was spasticity assessed by Modified Ashworth Scale or Ashworth Scale for lower limbs. The secondary outcome measures were walking abilities, such as 6 Min Walk Test (6MWT), Timed Up and Go (TUG), and lower limbs muscle strength (LEMS). A subgroup analysis was performed to investigate the efficacious threshold number of training sessions. A meta-regression analysis was used to examine the linear relationship between the training sessions and the effect on spasticity.Results: A total of 764 studies were identified. After screening, 12 selected studies were used for the qualitative synthesis, in which eight of them were quantitatively analyzed. Eight studies included ninety-nine subjects in total with SCI (male: female = 83:16). The time since injury was from less than 4 weeks to 17 years. The age ranged from 20 to 67 years. American Spinal Injury Association (ASIA) impairment level of the number of participants was 59 for ASIA A, 11 for ASIA B, 18 for ASIA C, and 11 for ASIA D. There were 43 subjects with tetraplegia and 56 subjects with paraplegia. Spasticity decreased significantly (95% CI = − 1.538 to − 0.182, p = 0.013) in favor of FES-cycling training. The walking ability and LEMS also improved significantly in favor of FES-cycling training. The subgroup analysis showed that spasticity decreased significantly only in more than 20 training sessions (95% CI = − 1.749 to − 0.149, p = 0.020). The meta-regression analysis showed training sessions and spasticity were not significantly associated (coefficient = − 0.0025, SE = 0.0129, p = 0.849, R2 analog = 0.37).Conclusion: Functional electrical stimulation-cycling training can improve spasticity, walking ability, and the strength of the lower limbs in the individuals with SCI. The number of training sessions is not linearly related to the decrease of spasticity. Twenty sessions of FES-cycling training are required to obtain the efficacy to decrease spasticity.

Introduction. Previous studies have shown that whole-body vibration (WBV) may have a potential impact on gait and balance in individuals with Parkinson’s disease (PD). However, this body of work has proven inconclusive due to the diverse disease progression and broad age range associated with PD. The effects of WBV on proprioception, a sense frequently affected by PD, has rarely been studied. Objective. To investigate the short-term effect of WBV on proprioception and motor function for individual with moderate PD. Design. A single-blind randomized controlled trial. Setting. A hospital and a laboratory. Participants. 32 participants with moderate PD were recruited and randomly assigned into either the WBV or conventional therapy groups. Interventions. For the WBV group, each treatment session included five, one-minute bouts of whole-body vibration paired with one-minute rest (frequency: 6 Hz; amplitude: 3 mm). Each conventional therapy participant received balance and mobility training for 10 minutes. Main Outcome Measures. Outcome measures included proprioceptive sensitivity of the upper limb, position sense of the knee joint, Unified Parkinson’s disease rating scale : motor section (UPDRS-motor), functional reach test (FRT), and the timed up and go test (TUG). Results. No statistically significant difference was found between groups. However, both groups showed a significant improvement in motor function after treatment, including UPDRS-motor (P=0.04), less affected side of FRT (P=0.019), and TUG (P=0.006). Conclusions. Although the effect of WBV was not superior to the conventional therapy, it provided a passive and safe clinical intervention as an alternative treatment, especially for individuals with motor impairment or poor balance function.

The heart is one of the human body’s vital organs. An electrocardiogram (ECG) provides continuous tracings of the electrophysiological activity originated from heart, thus being widely used for a variety of diagnostic purposes. This study aims to design and realize an artificial intelligence (AI)-based abnormal heart beat detection with applications for early detection and timely treatment for heart diseases. A convolutional neural network (CNN) was employed to achieve a fast and accurate identification. In order to meet the requirements of the modularity and scalability of the circuit, modular and efficient processing element (PE) units and activation function modules were designed. The proposed CNN was implemented using a TSMC 0.18 μm CMOS technology and had an operating frequency of 60 MHz with chip area of 1.42 mm2 and maximum power dissipation of 4.4 mW. Furthermore, six types of ECG signals drawn from the MIT-BIH arrhythmia database were used for performance evaluation. Results produced by the proposed hardware showed that the discrimination rate was 96.3% with high efficiency in calculation, suggesting that it may be suitable for wearable devices in healthcare.

Mutations in PLA2G6 gene cause PLA2G6-associated neurodegeneration, including recessive familial type 14 of Parkinson's disease (PARK14). Previously, we identified PARK14 patients with compound heterozygous c.991G > T/c.1077G > A (p.D331Y/p.M358IfsX) mutations. The c.1077G > A mutation led to a four base-pairs deletion and frameshift mutation (p.M358IfsX) of PLA2G6 mRNA. We established induced pluripotent stem cells (iPSCs) from peripheral blood mononuclear cells of a female patient with compound heterozygous c.991G > T/c.1077G > A (p.D331Y/ p.M358IfsX) mutations by using Sendai-virus delivery system. The iPSCs exhibited pluripotency and in vivo differentiation potential. The iPSCs can be used for studying the molecular pathogenic mechanism of PARK14.

MicroRNAs (miRs) downregulate or upregulate the mRNA level by binding to the 3′-untranslated region (3′UTR) of target gene. Dysregulated miR levels can be used as biomarkers of Parkinson’s disease (PD) and could participate in the etiology of PD. In the present study, 45 brain-enriched miRs were evaluated in serum samples from 50 normal subjects and 50 sporadic PD patients. The level of miR-204-5p was upregulated in serum samples from PD patients. An upregulated level of miR-204-5p was also observed in the serum and substantia nigra (SN) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Expression of miR-204-5p increased the level of α-synuclein (α-Syn), phosphorylated (phospho)-α-Syn, tau, or phospho-tau protein and resulted in the activation of endoplasmic reticulum (ER) stress in SH-SY5Y dopaminergic cells. Expression of miR-204-5p caused autophagy impairment and activation of c-Jun N-terminal kinase (JNK)-mediated apoptotic cascade in SH-SY5Y dopaminergic cells. Our study using the bioinformatic method and dual-luciferase reporter analysis suggests that miR-204-5p positively regulates mRNA expression of dual-specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) by directly interacting with 3′UTR of DYRK1A. The mRNA and protein levels of DYRK1A were increased in SH-SY5Y dopaminergic cells expressing miR-204-5p and SN of MPTP-induced PD mouse model. Knockdown of DYRK1A expression or treatment of the DYRK1A inhibitor harmine attenuated miR-204-5p-induced increase in protein expression of phospho-α-Syn or phospho-tau, ER stress, autophagy impairment, and activation of JNK-mediated apoptotic pathway in SH-SY5Y dopaminergic cells or primary cultured dopaminergic neurons. Our results suggest that upregulated expression of miR-204-5p leads to the death of dopaminergic cells by targeting DYRK1A-mediated ER stress and apoptotic signaling cascade.

Anticipatory postural adjustment (APA) existed before a self-induced perturbation is an important motor control skill for balance and gait initiation, but cannot be easily monitored. During proactive balance test, a self-initiated weight shifting is produced. This might be an optimal paradigm for APA measurement. The purpose of this study was to investigate if APAs existed in the proactive balance test which consists of quantifiable weight shifting. The feature and reliability of the APAs were also evaluated. We firstly built a proactive balance test program on the commercially available Wii balance board. The program could generate adjustable target direction and distance for guiding subjects performing quantifiable weight shifting. The center of pressure (COP) was recorded and analyzed for balance-related variables (path length, path time, and direction error) and APA-related variables (APA time, APA distance, and APA correction). The results showed that APAs could be detected in every testing trial. Adequate to good reliability in both balance and APA-related variables were found. This study proved the feasibility of quantifying APA during proactive balance tests and its feasibility for clinical- and home-based measurements.

Paroxysmal kinesigenic dyskinesia (PKD) is conventionally regarded as a movement disorder (MD) and characterized by episodic hyperkinesia by sudden movements. However, patients of PKD often have sensory aura and respond excellently to antiepileptic agents. PRRT2 mutations, the most common genetic etiology of PKD, could cause epilepsy syndromes as well. Standing in the twilight zone between MDs and epilepsy, the pathogenesis of PKD is unclear. Gamma oscillations arise from the inhibitory interneurons which are crucial in the thalamocortical circuits. The role of synchronized gamma oscillations in sensory gating is an important mechanism of automatic cortical inhibition. The patterns of gamma oscillations have been used to characterize neurophysiological features of many neurological diseases, including epilepsy and MDs. This study was aimed to investigate the features of gamma synchronizations in PKD. In the paired-pulse electrical-stimulation task, we recorded the magnetoencephalographic data with distributed source modeling and time-frequency analysis in 19 patients of newly-diagnosed PKD without receiving pharmacotherapy and 18 healthy controls. In combination with the magnetic resonance imaging, the source of gamma oscillations was localized in the primary somatosensory cortex. Somatosensory evoked fields of PKD patients had a reduced peak frequency (p < 0.001 for the first and the second response) and a prolonged peak latency (the first response p = 0.02, the second response p = 0.002), indicating the synchronization of gamma oscillation is significantly attenuated. The power ratio between two responses was much higher in the PKD group (p = 0.013), indicating the incompetence of activity suppression. Aberrant gamma synchronizations revealed the defective sensory gating of the somatosensory area contributes the pathogenesis of PKD. Our findings documented disinhibited cortical function is a pathomechanism common to PKD and epilepsy, thus rationalized the clinical overlaps of these two diseases and the therapeutic effect of antiepileptic agents for PKD. There is a greater reduction of the peak gamma frequency in PRRT2-related PKD than the non-PRRT PKD group (p = 0.028 for the first response, p = 0.004 for the second response). Loss-of-function PRRT2 mutations could lead to synaptic dysfunction. The disinhibiton change on neurophysiology reflected the impacts of PRRT2 mutations on human neurophysiology.

Intermittent theta burst stimulation (iTBS), a patterned repetitive transcranial magnetic stimulation, was applied over the posterior superior temporal sulcus (pSTS) or dorsolateral prefrontal cortex (DLPFC) to explore its impact in adults with autism spectrum disorder (ASD). Among 25 adults with ASD, 19 (mean age: 20.8 years) completed the randomized, sham-controlled, crossover trial. Every participant received iTBS over the bilateral DLPFC, bilateral pSTS and inion (as a sham control stimulation) in a randomized order with a 1-week interval. Neuropsychological functions were assessed using the Conners' Continuous Performance Test (CCPT) and the Wisconsin Card Sorting Test (WCST). Behavioral outcomes were measured using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Social Responsiveness Scale (SRS). In comparison to that in the sham stimulation, the reaction time in the CCPT significantly decreased following single DLPFC session (p = 0.04, effect size = 0.71) while there were no significant differences in the CCPT and WCST following single pSTS session. Besides, the results in behavioral outcomes were inconsistent and had discrepancy between reports of parents and patients. In conclusion, a single session of iTBS over the bilateral DLPFC may alter the neuropsychological function in adults with ASD. The impacts of multiple-sessions iTBS over the DLPFC or pSTS deserve further investigations.

This study investigated the neuromagnetic activities of self-paced finger lifting task and electrical median nerve stimulation in ten writer's cramp patients and fourteen control subjects. The event-related de/synchronizations (ERD/ERS) of beta-band activity levels were evaluated and the somatosensory cortical activity levels were analyzed using equivalent-current dipole modeling. No significant difference between the patients and control subjects was found in the electrical stimulation-induced beta ERS and electrical evoked somatosensory cortical responses. Movement-related beta ERD did not differ between controls and patients. Notably, the amplitude of the beta ERS after termination of finger movement was significantly lower in the patients than in the control subjects. The reduced movement-related beta ERS might reflect an impairment of motor cortex deactivation. In conclusion, a motor dependent dysregulation of the sensorimotor network seems to be involved in the functional impairment of patients with writer's cramp.

Study objectiveTo explore the profile of patients who visit a sleep center with symptoms that fulfill the four essential criteria for restless legs syndrome (RLS).DesignA prospective study.SettingOutpatients from one sleep disorders clinic in Taiwan.Participants1,200 consecutive patients visit sleep disorders clinic with any sleep complaints.InterventionsAfter completing a history and physical examination, all participants answered the RLS questionnaire. Subjects who fulfilled the four essential criteria for RLS were referred to a special clinic. A work-up including blood tests, polysomnography, and specialized neurological tests etc. was performed to make the final diagnosis.Measurements and resultsA total of 1,185 participants were enrolled, and, of these, 131(11.1%) fulfilled the four essential criteria for RLS, and 121 completed the supplemental work-up. Their mean age was 47.6±13.3 and 52.9% were male. Insomnia and snoring were the most common chief complaints. Obstructive sleep apnea syndrome and other diseases were found in 103 patients. Only 18 (14.9%) patients had no comorbid condition and were diagnosed with primary RLS.ConclusionsSymptoms of RLS are common in patients with sleep complaints. Even in a sleep clinic, using a questionnaire approach for identification of RLS has a low positive predictive value. Clinicians should pay attention to the limitations of the 4-item questionnaire in diagnosis of RLS and also the importance of a careful differential diagnosis to identify possible secondary causes of RLS.

Daily sessions of therapeutic transcranial brain stimulation are thought to prolong or amplify the effect of a single intervention. Here we show in patients with focal hand dystonia that additional, new effects build up progressively over time, making it difficult to predict the effect of long term interventions from shorter treatment sessions. In a sham-controlled study, real or sham continuous theta burst stimulation (cTBS) was given once daily for five consecutive days to dorsolateral premotor cortex (PMd). Five days of real, but not sham, premotor cTBS improved intracortical inhibition in primary motor cortex (M1) to a similar extent on day 1 and day 5. However 5 days of cTBS were required to restore the abnormal PMd-M1 interactions observed on day 1. Similarly, excessive M1 plasticity seen at baseline was also significantly reduced by five days of real premotor cTBS. There was only a marginal benefit on writing. The results show that additional, new effects, at sites distant from the point of stimulation, build up progressively over time, making it difficult to predict the effect of long term interventions from shorter treatment sessions. The results indicate that it may take many days of therapeutic intervention to rebalance activity in a complex network.