Stepwise Dual-Target Magnetic Resonance-Guided Focused Ultrasound in Tremor-Dominant Parkinson Disease: A Feasibility Study.

BACKGROUND: Magnetic resonance-guided focused ultrasound (MRgFUS) has been applied successfully in treating refractory tremors in Parkinson disease (PD). It generates a precise thermal ablation in a specific nucleus or tract, such as ventral intermediate nucleus (VIM) or pallidothalamic tract (PTT). Despite a single lesion improving parts of the PD symptoms, the feasibility and efficacy of a stepwise dual-lesion in VIM and PTT are yet to be explored. METHODS: Three patients with tremor-dominant PD (aged 60.7 ± 6.0 years) received dual-target MRgFUS treatment with a series of primary and secondary outcome measures. The VIM and PTT were navigated based on individual magnetic resonance imaging planning of the brain. The primary outcome measures were the off-status Clinical Rating Scale for Tremor and Unified Parkinson's Disease Rating Scale part III (UPDRS-III). The secondary outcome measures included UPDRS I, II, IV, Hohen and Yahr score, Neuropsychiatry Inventory, Quality of life in PD Rating Scale, Non-Motor Symptoms Scale, and Clinical Global Impression. The baseline data were compared with those acquired 1 day and 1 month following the treatment. RESULTS: The severity of tremor and motor deficits represented by Clinical Rating Scale for Tremor-part B and UPDRS III were significantly improved (P < 0.05 by nonparametric Mann-Whitney U tests) after dual-target ablations. The nonmotor symptoms investigated by UPDRS II and Non-Motor Symptoms Scale also showed significant improvement at the 1-day and 1-month follow-up. There was no adverse effect except temporary procedure-related headache and dizziness during the treatment. CONCLUSIONS: Stepwise dual-lesion targeting VIM and PTT is a safe and effective MRgFUS therapeutic strategy for patients with PD.

Efficiency of an Online Health-Promotion Program in Individuals with At-Risk Mental State during the COVID-19 Pandemic.

Mental health issues caused by the COVID-19 pandemic greatly impact people's daily lives. Individuals with an at-risk mental state are more vulnerable to mental health issues, and these may lead to onset of full psychotic illnesses. This study aimed to develop and evaluate an online health-promotion program for physical and mental health of the individuals with at-risk mental state during the COVID-19 pandemic. A single group study with pre- and post-tests was conducted in 39 young adults with at-risk mental state. The participants were provided with the online health-promotion program after completing the pretest. Via social media, the online counseling program released one topic of material (about 15-20 min) every two weeks and provided interactive counseling for specific personal health needs on the platform. Study questionnaires, physiological examination, and blood serum examination were completed at both pre- and post-tests. The participants showed significant improvements in mental risk, anxiety, and physical activity after participating in the program. Furthermore, those who did not complete the program had significantly more severe negative symptoms. These results imply that the online health-promotion program is effective and accessible under certain barriers such as the COVID-19 pandemic, but not for individuals with higher risk of more negative mental health symptoms.

Gait-Related Brain Activation During Motor Imagery of Complex and Simple Ambulation in Parkinson's Disease With Freezing of Gait.

Background: Freezing of gait (FOG) in Parkinson's disease (PD) is a devastating clinical phenomenon that has a detrimental impact on patients. It tends to be triggered more often during turning (complex) than during forwarding straight (simple) walking. The neural mechanism underlying this phenomenon remains unclear and requires further elucidation. Objective: To investigate the differences in cerebral functional magnetic resonance imaging responses between PD patients with and without FOG during explicitly video-guided motor imagery (MI) of various complex (normal, freezing) and simple (normal, freezing) walking conditions. Methods: We recruited 34 PD patients, namely, 20 with FOG and 14 without FOG, and 15 normal controls. Participants underwent video-guided MI of turning and straight walking, with and without freezing, while their brain blood oxygen level-dependent (BOLD) activities were measured. Gait analysis was performed. Results: While comparing FOG turning with FOG straight walking, freezers showed higher activation of the superior occipital gyrus, left precentral gyrus, and right postcentral gyrus compared with non-freezers. Normal controls also manifest similar findings compared with non-freezers, except no difference was noted in occipital gyrus activity between the two groups. Freezers also displayed a higher effect size in the locomotor regions than non-freezers during imagery of normal turning. Conclusions: Our findings suggest that freezers require a higher drive of cortical and locomotion regions to overcome the overinhibition of the pathways in freezers than in non-freezers. Compared with simple walking, increased dorsal visual pathway and deep locomotion region activities might play pivotal roles in tackling FOG in freezers during complex walking.

Real-world Evaluation of Tolerability, Safety and Efficacy of Rivastigmine Oral Solution in Patients with Mild to Moderate Alzheimer's Disease Dementia.

OBJECTIVE: The purpose of this study is to investigate the safety, tolerability and efficacy of titrating dose of rivastigmine oral solution in patients with mild to moderate Alzheimer's disease (AD) in Taiwan. METHODS: We recruited 108 mild to moderate AD patients with RivastⓇ (rivastigmine oral solution 2 mg/ml) treatment for 52 weeks. We recorded the demographic characteristics, initial cognition by mini-mental state examination (MMSE), initial global status by clinical dementia rating (CDR) with CDR-Sum of Boxes (CDR-SB), initial dose, and titrating dose at each visit. We investigated the adherence, proportion of possible side effects, optimal dose, and time to optimal dose. We demonstrated the proportion of cognitive decline and its possible risk factors. RESULTS: During the course, 9 patients discontinued the rivastigmine oral solution due to poor compliance or preference. Twelve out of 99 patients (12.1%) reported possible side effects. Among 87 patients, the mean age was 77.2 ± 9.0 years ago with female predominant (65.2%). The optimal dose was 3.6 ± 1.4 ml in average and 4 ml (n = 31, 35.6%) in mode. The duration to optimal dose was 12.5 ± 10.2 weeks and 24 weeks (n = 35, 40.2%) in mode. It presented 25% with cognitive decline in MMSE, 27% with global function decline in CDR and 63% with global function decline in CDR-SB. CONCLUSION: We demonstrated the clinical experience of rivastigmine oral solution in mild to moderate AD patients. It suggested rivastigmine oral solution 4ml is the optimal dose with 24 weeks to the optimal dose for at least one third of patients.

Low-frequency oscillations in cortical level to help diagnose task-specific dystonia.

Task-specific dystonia is a neurological movement disorder that abnormal contractions of muscles result in the twisting of fixed postures or muscle spasm during specific tasks. Due to the rareness and the pathophysiology of the disease, there is no test to confirm the diagnosis of task-specific dystonia, except comprehensive observations by the experts. Evidence from neural electrophysiological data suggests that enhanced low frequency (4-12 Hz) oscillations in the subcortical structure of the globus pallidus were associated with the pathological abnormalities concerning ß and γ rhythms in motor areas and motor cortical network in patients with task-specific dystonia. However, whether patients with task-specific dystonia have any low-frequency abnormalities in motor cortical areas remains unclear. In this study, we hypothesized that low-frequency abnormalities are present in core motor areas and motor cortical networks in patients with task-specific dystonia during performing the non-symptomatic movements and those low-frequency abnormalities can help the diagnosis of this disease. We tested this hypothesis by using EEG, effective connectivity analysis, and a machine learning method. Fifteen patients with task-specific dystonia and 15 healthy controls were recruited. The machine learning method identified 8 aberrant movement-related network connections concerning low frequency, ß and γ frequencies, which enabled the separation of the data of patients from those of controls with an accuracy of 90%. Importantly, 7 of the 8 aberrant connections engaged the premotor area contralateral to the affected hand, suggesting an important role of the premotor area in the pathological abnormities. The patients exhibited significantly lower low frequency activities during the movement preparation and significantly lower ß rhythms during movements compared with healthy controls in the core motor areas. Our findings of low frequency- and ß-related abnormalities at the cortical level and aberrant motor network could help diagnose task-specific dystonia in the clinical setting, and the importance of the contralesional premotor area suggests its diagnostic potential for task-specific dystonia.

Bereitschaftspotential in Multiple System Atrophy.

Objective: Multiple system atrophy (MSA) is a neurodegenerative disorder manifesting as parkinsonism, cerebellar ataxia, and autonomic dysfunction. It is categorized into MSA with predominant parkinsonism (MSA-P) and into MSA with predominant cerebellar ataxia (MSA-C). The pathophysiology of motor control circuitry involvement in MSA subtype is unclear. Bereitschaftspotential (BP) is a feasible clinical tool to measure electroencephalographic activity prior to volitional motions. We recorded BP in patients with MSA-P and MSA-C to investigate their motor cortical preparation and activation for volitional movement. Methods: We included eight patients with MSA-P, eight patients with MSA-C, and eight age-matched healthy controls. BP was recorded during self-paced rapid wrist extension movements. The electroencephalographic epochs were time-locked to the electromyography onset of the voluntary wrist movements. The three groups were compared with respect to the mean amplitudes of early (1,500-500 ms before movement onset) and late (500-0 ms before movement onset) BP. Results: Mean early BP amplitude was non-significantly different between the three groups. Mean late BP amplitude in the two patient groups was significantly reduced in the parietal area contralateral to the movement side compared with that in the healthy control group. In addition, the late BP of the MSA-C group but not the MSA-P group was significantly reduced at the central parietal area compared with that of the healthy control group. Conclusions: Our findings suggest that patients with MSA exhibit motor cortical dysfunction in voluntary movement preparation and activation. The dysfunction can be practicably evaluated using late BP, which represents the cerebello-dentato-thalamo-cortical pathway.

The Distribution of Skull Score and Skull Density Ratio in Tremor Patients for MR-Guided Focused Ultrasound Thalamotomy.

OBJECTIVE: Magnetic resonance-guided focused ultrasound (MRgFUS) is a minimum-invasive surgical approach to non-incisionally cause the thermos-coagulation inside the human brain. The skull score (SS) has already been approved as one of the most dominant factors related to a successful MRgFUS treatment. In this study, we first reveal the SS distribution of the tremor patients, and correlate the SS with the image feature from customized skull density ratio (cSDR). This correlation might give a direction to future clinical studies for improving the SS. METHODS: Two hundred and forty-six patients received a computed tomography (CT) scan of the brain, and a bone-enhanced filter was applied and reconstructed to a high spatial resolution CT images. The SS of all patients would be estimated by the MRgFUS system after importing the reconstructed CT images into the MRgFUS system. The histogram and the cumulative distribution of the SS from all the patients were calculated to show the percentage of the patients whose SS lower than 0.3 and 0.4. The same CT images of all patients were utilized to calculated the cSDR by first segmented the trabecular bone and the cortical bone from the CT images and divided the average trabecular bone intensity (aTBI) by the average cortical bone intensity (aCBI). The Pearson's correlations between the SS and the cSDR, aTBI, and the aCBI were calculated, respectively. RESULTS: There were 19.19 and 50% of the patient who had the SS lower than the empirical threshold 0.3 and 0.4, respectively. The Pearson's correlation between the SS and the cSDR, aCBI, and the aTBI were R = 0.8145, 0.5723, and 0.8842. CONCLUSION: Half of the patients were eligible for the MRgFUS thalamotomy based on the SS, and nearly 20% of patients were empirically difficult to achieve a therapeutic temperature during MRgFUS. The SS and our cSDR are highly correlated, and the SS had a higher correlation with aTBI than with aCBI. This is the first report to explicitly reveal the SS population and indicate a potential way to increase the chance to achieve a therapeutic temperature for those who originally have low SS.

Low-Parameter Small Convolutional Neural Network Applied to Functional Medical Imaging of Tc-99m Trodat-1 Brain Single-Photon Emission Computed Tomography for Parkinson's Disease.

Parkinson's disease (PD), a progressive disease that affects movement, is related to dopaminergic neuron degeneration. Tc-99m Trodat-1 brain (TRODAT) single-photon emission computed tomography (SPECT) aids the functional imaging of dopamine transporters and is used for dopaminergic neuron enumeration. Herein, we employed a convolutional neural network to facilitate PD diagnosis through TRODAT SPECT, which is simpler than models such as VGG16 and ResNet50. We retrospectively collected the data of 3188 patients (age range 20-107 years) who underwent TRODAT SPECT between June 2011 and December 2019. We developed a set of functional imaging multiclassification deep learning algorithms suitable for TRODAT SPECT on the basis of the annotations of medical experts. We then applied our self-proposed model and compared its results with those of four other models, including deep and machine learning models. TRODAT SPECT included three images collected from each patient: one presenting the maximum absorption of the metabolic function of the striatum and two adjacent images. An expert physician determined that our model's accuracy, precision, recall, and F1-score were 0.98, 0.98, 0.98, and 0.98, respectively. Our TRODAT SPECT model provides an objective, more standardized classification correlating to the severity of PD-related diseases, thereby facilitating clinical diagnosis and preventing observer bias.

Changes in Balance, Gait and Electroencephalography Oscillations after Robot-Assisted Gait Training: An Exploratory Study in People with Chronic Stroke.

Robot-assisted gait training (RAGT) systems offer the advantages of standard rehabilitation and provide precise and quantifiable control of therapy. We examined the clinical outcome of RAGT and analyzed the correlations between gait analysis data and event-related desynchronization (ERD) and event-related synchronization (ERS) in patients with chronic stroke. We applied the Berg balance scale (BBS) and analyzed gait parameters and the ERD and ERS of self-paced voluntary leg movements performed by patients with chronic stroke before and after undergoing RAGT. A significant change was observed in BBS (p = 0.011). We also showed preliminary outcomes of changes in gait cycle duration (p = 0.015) and in ipsilesional ERS in the low-beta (p = 0.033) and high-beta (p = 0.034) frequency bands before and after RAGT. In addition, correlations were observed between BBS and ipsilesional ERS in the alpha and low-beta bands (r = -0.52, p = 0.039; r = -0.52, p = 0.040). The study demonstrated that RAGT can improve balance and provided an idea of the possible role of brain oscillation and clinical outcomes in affecting stroke rehabilitation.

Convergent Associative Motor Cortical Plasticity Induced by Conditional Somatosensory and Motor Reaction Afferents.

Objective: Associative motor cortical plasticity can be non-invasively induced by paired median nerve electric stimulation and transcranial magnetic stimulation (TMS) of the primary motor cortex (M1). This study investigates whether a simultaneous motor reaction of the other hand advances the associative plasticity in M1. Methods: Twenty-four right-handed subjects received conventional paired associative stimulation (PAS) and PAS with simultaneous motor reaction (PASmr) with at least a 1-week interval. The PASmr protocol additionally included left abductor pollicis brevis muscle movement responding to a digital sound. The motor reaction time was individually measured. The M1 excitability was examined by the motor evoked potential (MEP), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) before and after the PAS protocols. Results: The conventional PAS protocol significantly facilitated MEP and suppressed SICI. A negative correlation between the reaction time and the MEP change, and a positive correlation between the reaction time and the ICF change were found in the PASmr protocol. By subgrouping analysis, we further found significant facilitation of MEP and a reduction of ICF in the subjects with fast reaction times but not in those with slow reaction times. Conclusion: Synchronized motor reaction ipsilateral to the stimulated M1 induces associative M1 motor plasticity through the spike-timing dependent principle. MEP and ICF change could represent this kind of plasticity. The current findings provide a novel insight into designing rehabilitation programs concerning motor function.

Impairments in face discrimination and emotion recognition are related to aging and cognitive dysfunctions in Parkinson's disease with dementia.

Patients with Parkinson's disease (PD) suffer from motor and non-motor symptoms; 40% would develop dementia (PD-D). Impaired face and emotion processing in PD has been reported; however, the deficits of face processing in PD-D remain unclear. We investigated three essential aspects of face processing capacity in PD-D, and the associations between cognitive, neuropsychiatric assessments and task performances. Twenty-four PD-D patients (mean age: 74.0 ± 5.55) and eighteen age-matched healthy controls (HC) (mean age: 71.0 ± 6.20) received three computerized tasks, morphing-face discrimination, dynamic facial emotion recognition, and expression imitation. Compared to HC, PD-D patients had lower sensitivity (d') and greater neural internal noises in discriminating faces; responded slower and had difficulties with negative emotions; imitated some expressions but with lower strength. Correlation analyses revealed that patients with advancing age, slow mentation, and poor cognition (but not motor symptoms) showed stronger deterioration in face perception. Importantly, these correlations were absent in the age-matched HC. The present study is among the first few examined face processing in patients with PD-D, and found consistent deficits correlated with advancing age and slow mentation. We propose that face discrimination task could be included as a potential test for the early detection of dementia in PD.

Event-Related Desynchronization/Synchronization in Spinocerebellar Ataxia Type 3.

Introduction: Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant, cerebellar degeneration predominant disease caused by excessive CAG repeats. We examined event-related dysynchronization/synchronization (ERD/ERS) in patients with SCA3. Methods: We assessed ERD/ERS of self-paced voluntary hand movements in 15 patients with genetically proven SCA3 in comparison with healthy controls. Results: In ERS, a significant interaction effect between group, frequency, and period (F = 1.591; p = 0.005; ρI = 0.86) was observed. The post-hoc two-tailed independent t-test showed significant differences in high beta and low beta ERS. By contrast, in ERD, no apparent differences were observed in the pattern of patients with SCA3 in comparison with healthy controls (F = 1.01; p = 0.442). Conclusion: The study revealed a decreased ERS in patients with SCA3, especially at the frequency of 20-30 Hz. This study elucidates the significant role of cerebellum in motor control.

Peripheral trauma and risk of dystonia: What are the evidences and potential co-risk factors from a population insurance database?

BACKGROUND: Dystonia is a neurological syndrome typically resulting in abnormal postures. OBJECTIVES: We tested the role of physical injury as potential risk factor for development of dystonia using The National Health Insurance Research Database of Taiwan. METHODS: We identified 65704 people who were coded in the database as having had peripheral traumatic injuries (ICD-9-CM 807-848 and 860-959) in the year 2000. Patients with traumatic brain or spine injuries were excluded from analysis. We matched them using purposive sampling with 65704 people in the database who had not suffered peripheral trauma. We looked then at the incidence of dystonia occurring at least 1 year from the date of the peripheral trauma until 2011. Psychiatric symptoms (depression and anxiety) and sleeps difficulties have been investigated as potential covariates. RESULTS: We found 189 patients with dystonia (0.28%) in the trauma group, and 52 patients with dystonia (0.08%) in the non-trauma group. Trauma was independently associated with dystonia (adjusted HR = 3.12, 95% CI = 2.30-4.24). The incidence density of dystonia in the trauma group was 2.27 per 10000 person-years, while it was 0.71 per 10000 person-years in the non-trauma group Beyond the peripheral trauma, other variables associated to the incidence of dystonia included female sex, aged 40 years and above, depression and sleep disorders. CONCLUSION: These data from a large population dataset support traumatic injury as a risk factor for the development of dystonia.

Paired Associative Electroacupuncture and Transcranial Magnetic Stimulation in Humans.

Pairing transcutaneous electric nerve stimulation (TENS) and transcranial magnetic stimulation (TMS) with specific stimulus-intervals induces associative motor plasticity at the primary motor cortex (M1). Electroacupuncture (EA) is an established medical technique in the eastern countries. This study investigates whether EA paired with TMS induces distinct M1 motor plasticity. Fifteen healthy, right-handed subjects (aged 23.6 ± 2.0 years, eight women) were studied. Two-hundred and twenty-five pairs of TMS of the left M1 preceded by right EA at acupoint "Neiguan" [Pericardium 6 (PC6), located 2 decimeters proximal from the wrist wrinkle] were respectively applied with the interstimulus interval (ISI) of individual somatosensory evoked potential (SSEP) N20 latency plus 2 ms (N20+2) and minus 5 ms (N20-5) with at least 1-week interval. The paired stimulation was delivered at a rate of 0.25 Hz. Sham TMS with a sham coil was adopted to examine the low-frequency EA influence on M1 in eleven subjects. M1 excitability was assessed by motor-evoked potential (MEP) recruitment curve with five TMS intensity levels, short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and cerebellar inhibition (CBI) at the abductor pollicis brevis (APB) muscle of the right hand before and after the EA-M1 paired associative stimulation (PAS). In addition, median nerve SSEPs and H-reflex were respectively measured to monitor somatosensory and spinal excitability. The MEP showed significantly facilitated after the sham EA-M1 PAS while tested with 80% of the TMS intensity producing on average 1 mV amplitude (i.e., MEP1 mV) in the resting APB muscle. It was also facilitated while tested with 90% MEP1 mV irrespective of the stimulation conditions. The SSEP showed a higher amplitude from the real EA-M1 PAS compared to that from the sham EA-M1 PAS. No significant change was found on SICI, ICF, CBI and H-reflex. Findings suggest that repetitive low frequency EA paired with real TMS did not induce spike-timing dependent motor plasticity but EA paired with sham TMS induced specific M1 excitability change. Complex sensory afferents with dispersed time locked to the sensorimotor cortical area could hamper instead of enhancing the induction of the spike-timing dependent plasticity (STDP) in M1.

Improving Automatic Tremor and Movement Motor Disorder Severity Assessment for Parkinson's Disease with Deep Joint Training.

Parkinson's disease (PD) is one of the most severe and common disease globally. PD induces motor system impairment causing symptoms such as shaking, rigidity, slowness of movement, body tremor and difficulty with walking. Clinically, accurately and objectively assessing the severity of PD symptoms is critical in controlling appropriate dosage of Levodopa to prevent unwanted side effect of switching between Dyskinesia and PD. The unified Parkinson's disease rating scale published by the Movement Disorder Society (MDS-UPDRS) is an validated instrument regularly administrated by trained physician to assess the severity of a PD patient's motor disorder. In this work, we aim at advancing vision-based automatic motor disorder assessment, specifically hand tremor and movement, for PD patients during UPDRS. Our proposed method leverages information across the two behavior tasks simultaneously via deep joint training to improve each single task's, i.e., tremor and movement, severity classification rate. We evaluate our framework on a large cohort of 106 PD patients, and with our proposed deep joint training framework, we achieve accuracy of 78.01% and 80.60% in right and left hand movement binary classification; in terms of tremor severity classification, our approach obtains an enhanced recognition rates of 72.20% and 71.10% for right and left hand respectively.

Delineating cerebellar mechanisms in DYT11 myoclonus-dystonia.

BACKGROUND: Recent research has highlighted the role of the cerebellum in the pathophysiology of myoclonus-dystonia syndrome as a result of mutations in the ɛ-sarcoglycan gene (DYT11). Specifically, a cerebellar-dependent saccadic adaptation task is dramatically impaired in this patient group. OBJECTIVES: The objective of this study was to investigate whether saccadic deficits coexist with impairments of limb adaptation to provide a potential mechanism linking cerebellar dysfunction to the movement disorder within symptomatic body regions. METHODS: Limb adaptation to visuomotor (visual feedback rotated by 30°) and forcefield (force applied by robot to deviate arm) perturbations were examined in 5 patients with DYT11 and 10 aged-matched controls. RESULTS: Patients with DYT11 successfully adapted to both types of perturbation. Modelled and averaged summary metrics that captured adaptation behaviors were equivalent to the control group across conditions. CONCLUSIONS: DYT11 is not characterized by a uniform deficit in adaptation. The previously observed large deficit in saccadic adaption is not reflected in an equivalent deficit in limb adaptation in symptomatic body regions. We suggest potential mechanisms at the root of this discordance and identify key research questions that need future study. © 2018 International Parkinson and Movement Disorder Society.

Multispecies probiotics combination prevents ovalbumin-induced airway hyperreactivity in mice

BACKGROUND: Probiotics could be beneficial to health and some of them have shown to modulate immune responses. AIM: The aim of this study is to investigate if the probiotic strains including Lactobacillus and Pediococcus strains are able to alleviate allergic reactions in an ovalbumin-induced airway allergy model. METHODS: Lactobacillus multi-species preparation (LMP) was gavaged to BALB/c for total six weeks and BALB/c was challenged with ovalbumin in the last two weeks. A barometric whole-body plethysmography was used to assess enhanced pause (Penh) of airway hyperreactivity (AHR). Immunoglobulins (Ig) such as IgE, IgG1, IgG2a and cytokines such as IL-12, IFN-gamma, IL-4, IL-5, TNF-alfa and IL-13 in bronchoalveolar lavage fluid were assayed using ELISA kits. RESULTS: The results showed this LMP significantly reduced Th2 cytokines and enhanced Th1 cytokines production. OVA-specific IgE and IgG1 was lower in the probiotics-treated mice whereas IgG2a was increased. Most importantly, this murine model showed LMP supplementation significantly reduced AHR. CONCLUSIONS: Overall, this Lactobacillus multi-species preparation seemed to suppress OVA-sensitized airway hyperreactivity, thus serving as a possible candidate for therapeutic uses for allergic airway symptoms

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Cervical dystonia: Normal auditory mismatch negativity and abnormal somatosensory mismatch negativity.

OBJECTIVE: Previous electrophysiological and psychophysical tests have suggested that somatosensory integration is abnormal in dystonia. Here, we hypothesised that this abnormality could relate to a more general deficit in pre-attentive error/deviant detection in patients with dystonia. We therefore tested patients with dystonia and healthy subjects using a mismatch negativity paradigm (MMN), where evoked potentials generated in response to a standard repeated stimulus are subtracted from the responses to a rare "odd ball" stimulus. METHODS: We assessed MMN for somatosensory and auditory stimuli in patients with cervical dystonia and healthy age matched controls. RESULTS: We found a significant group ∗ oddball type interaction effect (F (1, 34) = 4.5, p = 0.04, ρI = 0.63). A follow up independent t-test for sMMN data, showed a smaller sMMN amplitude in dystonic patients compared to controls (mean difference control-dystonia: -1.0 µV ± 0.3, p < 0.00, t = -3.1). However the amplitude of aMMN did not differ between groups (mean difference control-dystonia: -0.2 µV ± 0.2, p = 0.24, t = -1.2). We found a positive correlation between somatosensory MMN and somatosensory temporal discrimination threshold. CONCLUSION: These results suggest that pre-attentive error/deviant detection, specifically in the somatosensory domain, is abnormal in dystonia. This could underlie some previously reported electrophysiological and psychophysical abnormalities of somatosensory integration in dystonia. SIGNIFICANCE: One could hypothesize a deficit in pre-conscious orientation towards potentially salient signals might lead to a more conservative threshold for decision-making in dystonia.

Multispecies probiotics combination prevents ovalbumin-induced airway hyperreactivity in mice.

BACKGROUND: Probiotics could be beneficial to health and some of them have shown to modulate immune responses. AIM: The aim of this study is to investigate if the probiotic strains including Lactobacillus and Pediococcus strains are able to alleviate allergic reactions in an ovalbumin-induced airway allergy model. METHODS: Lactobacillus multi-species preparation (LMP) was gavaged to BALB/c for total six weeks and BALB/c was challenged with ovalbumin in the last two weeks. A barometric whole-body plethysmography was used to assess enhanced pause (Penh) of airway hyperreactivity (AHR). Immunoglobulins (Ig) such as IgE, IgG1, IgG2a and cytokines such as IL-12, IFN-γ, IL-4, IL-5, TNF-α and IL-13 in bronchoalveolar lavage fluid were assayed using ELISA kits. RESULTS: The results showed this LMP significantly reduced Th2 cytokines and enhanced Th1 cytokines production. OVA-specific IgE and IgG1 was lower in the probiotics-treated mice whereas IgG2a was increased. Most importantly, this murine model showed LMP supplementation significantly reduced AHR. CONCLUSIONS: Overall, this Lactobacillus multi-species preparation seemed to suppress OVA-sensitized airway hyperreactivity, thus serving as a possible candidate for therapeutic uses for allergic airway symptoms.

Effect of Transcranial Direct Current Stimulation in Patients With Tinnitus: A Meta-Analysis and Systematic Review.

OBJECTIVES: Subjective tinnitus is a phantom sensation experienced without any external source of sound that profoundly impacts the quality of life. Some investigations have claimed that transcranial direct current stimulation (tDCS) reduces tinnitus, but studies on tDCS have demonstrated variable results. This meta-analysis aimed to examine the effect of tDCS on patients with tinnitus. METHODS: We searched for articles published through January 5, 2016, in Medline, Cochrane, EMBASE, and Google Scholar using the following keywords: tinnitus, transcranial direct current stimulation, and tDCS. The study outcomes were change in magnitude estimates of loudness (loudness), tinnitus-related distress (distress), and Tinnitus Handicap Inventory (THI). RESULTS: Pooled results demonstrated that tDCS did not have a beneficial effect on loudness (pooled standardized difference in means = 0.674, 95% CI, -0.089 to 1.437, P = .083). Further, the pooled results demonstrated a greater reduction in distress for the tDCS group (pooled standardized difference in means = 0.634, 95% CI, 0.021-1.247, P = .043). CONCLUSIONS: We conclude that the pooled results demonstrated a greater reduction in distress for groups treated with tDCS as compared with those administered a sham treatment.