Machado-Joseph disease (MJD) belongs to a group of genetic diseases with expanded trinucleotide repeats and is a neurodegenerative disease affecting multiple systems with heterogeneous phenotypic manifestations.^1-4 Although the number of trinucleotide repeats inversely correlates with the age at onset,^5-7 the relationship between genotype and clinical manifestations, particularly autonomic functions, is unclear.

Transcranial focused ultrasound (tFUS) is a novel neuromodulating technique. It has been demonstrated that the neuromodulatory effects can be induced by weak ultrasound exposure levels (spatial-peak temporal average intensity, I_SPTA < 10 mW/cm²) in vitro. However, fewer studies have examined the use of weak tFUS to potentially induce long-lasting neuromodulatory responses in vivo. The purpose of this study was to determine the lower-bound threshold of tFUS stimulation for inducing neuromodulation in the motor cortex of rats. A total of 94 Sprague–Dawley rats were used. The sonication region aimed at the motor cortex under weak tFUS exposure (I_SPTA of 0.338–12.15 mW/cm²). The neuromodulatory effects of tFUS on the motor cortex were evaluated by the changes in motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS). In addition to histology analysis, the in vitro cell culture was used to confirm the neuromodulatory mechanisms following tFUS stimulation. In the results, the dose-dependent inhibitory effects of tFUS were found, showing increased intensities of tFUS suppressed MEPs and lasted for 30 min. Weak tFUS significantly decreased the expression of excitatory neurons and increased the expression of inhibitory GABAergic neurons. The PIEZO-1 proteins of GABAergic neurons were found to involve in the inhibitory neuromodulation. In conclusion, we show the use of weak ultrasound to induce long-lasting neuromodulatory effects and explore the potential use of weak ultrasound for future clinical neuromodulatory applications.

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 $\mathsf{\mu }$m CMOS technology and had an operating frequency of 60 MHz with chip area of 1.42 mm${}^2$ 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.

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.

Introduction: REM 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.Methods: By 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.Results: The 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.Conclusion: We 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.