Unlocking the potential: T1-weighed MRI as a powerful predictor of levodopa response in Parkinson's disease.

BACKGROUND: The efficacy of levodopa, the most crucial metric for Parkinson's disease diagnosis and treatment, is traditionally gauged through the levodopa challenge test, which lacks a predictive model. This study aims to probe the predictive power of T1-weighted MRI, the most accessible modality for levodopa response. METHODS: This retrospective study used two datasets: from the Parkinson's Progression Markers Initiative (219 records) and the external clinical dataset from Ruijin Hospital (217 records). A novel feature extraction method using MedicalNet, a pre-trained deep learning network, along with three previous approaches was applied. Three machine learning models were trained and tested on the PPMI dataset and included clinical features, imaging features, and their union set, using the area under the curve (AUC) as the metric. The most significant brain regions were visualized. The external clinical dataset was further evaluated using trained models. A paired one-tailed t-test was performed between the two sets; statistical significance was set at p < 0.001. RESULTS: For 46 test set records (mean age, 62 ± 9 years, 28 men), MedicalNet-extracted features demonstrated a consistent improvement in all three machine learning models (SVM 0.83 ± 0.01 versus 0.73 ± 0.01, XgBoost 0.80 ± 0.04 versus 0.74 ± 0.02, MLP 0.80 ± 0.03 versus 0.70 ± 0.07, p < 0.001). Both feature sets were validated on the clinical dataset using SVM, where MedicalNet features alone achieved an AUC of 0.64 ± 0.03. Key responsible brain regions were visualized. CONCLUSION: The T1-weighed MRI features were more robust and generalizable than the clinical features in prediction; their combination provided the best results. T1-weighed MRI provided insights on specific regions responsible for levodopa response prediction. CRITICAL RELEVANCE STATEMENT: This study demonstrated that T1w MRI features extracted by a deep learning model have the potential to predict the levodopa response of PD patients and are more robust than widely used clinical information, which might help in determining treatment strategy. KEY POINTS: This study investigated the predictive value of T1w features for levodopa response. MedicalNet extractor outperformed all other previously published methods with key region visualization. T1w features are more effective than clinical information in levodopa response prediction.

High-sensitivity vector magnetic field sensor based on a V-shaped multimode-no-core-multimode fiber structure.

This work proposes and investigates a bent multimode-no-core-multimode optical fiber structure for vector magnetic field sensing applications. The bent no-core fiber (NCF) serves as the sensing area, and the gold film is deposited on its surface to excite the surface plasmon resonance effect. Due to the strong evanescent field of the unclad and bent NCF, the as-fabricated sensor exhibits a high sensitivity of 5630 nm/RIU in the refractive index range of 1.36-1.39. Magnetic fluid is employed as the magneto-sensitive material for magnetic field sensing, exhibiting a high magnetic field intensity sensitivity of 5.74 nm/mT and a high magnetic field direction sensitivity of 0.22 nm/°. The proposed sensor features a simple structure, low cost, point sensing, and excellent mechanical performance.

Indirect Impact of Eutrophication on Occurrence, Air-Water Exchange, and Vertical Sinking Fluxes of Antibiotics in a Subtropical River.

A significant challenge that warrants attention is the influence of eutrophication on the biogeochemical cycle of emerging contaminants (ECs) in aquatic environments. Antibiotics pollution in the eutrophic Pearl River in South China was examined to offer new insights into the effects of eutrophication on the occurrence, air-water exchange fluxes (Fair-water), and vertical sinking fluxes (Fsinking) of antibiotics. Antibiotics transferred to the atmosphere primarily through aerosolization controlled by phytoplankton biomass and significant spatiotemporal variations were observed in the Fair-water of individual antibiotics throughout all sites and seasons. The Fsinking of ∑AB14 (defined as a summary of 14 antibiotics) was 750.46 ± 283.19, 242.71 ± 122.87, and 346.74 ± 249.52 ng of m-2 d-1 in spring, summer, and winter seasons. Eutrophication indirectly led to an elevated pH, which reduced seasonal Fair-water of antibiotics, sediment aromaticity, and phytoplankton hydrophobicity, thereby decreasing antibiotic accumulation in sediments and phytoplankton. Negative correlations were further found between Fsinking and the water column daily loss of antibiotics with phytoplankton biomass. The novelty of this study is to provide new complementary knowledge for the regulation mechanisms of antibiotics by phytoplankton biological pump, offering novel perspectives and approaches to understanding the coupling between eutrophication and migration and fate of antibiotics in a subtropical eutrophic river.

Superior cerebellar peduncle deep brain stimulation for cerebral palsy.

OBJECTIVE: Patients with coexisting spastic cerebral palsy (CP) and dystonia have limited treatment options. In this study, the authors aimed to evaluate the efficacy of deep brain stimulation (DBS) targeting the superior cerebellar peduncles (SCPs) in adults with CP. METHODS: Five patients with CP and medically refractory dystonia and spasticity underwent SCP DBS. Assessments included the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), modified Ashworth scale (mAS), and tests of cognition, mental status, and quality of life preoperatively and at 3, 6, and 12 months postoperatively (in both DBS ON and OFF states, double blinded). Active contacts and fiber bundles were examined. RESULTS: Four patients completed follow-up. The BFMDRS motor score decreased from 74 to 52 at 12 months postoperatively (30%, p = 0.008). The mean mAS score indicated significant spasticity reduction (from 2.9 ± 0.9 to 1.9 ± 0.6 after 12 months, p = 0.0454). Quality of life improved (p < 0.01), while cognition remained unaffected. Active contacts were found within the dentato-rubro-thalamic tract, with variable efficiency in decussating and nondecussating portions. CONCLUSIONS: In this pilot trial, SCP DBS showed promise as a well-tolerated treatment for CP, improving dystonic symptoms, spasticity, quality of life, and functional capacities. However, caution is needed when interpreting the results given the small sample size and heterogeneous motor outcomes.

Iron and neuromelanin imaging in basal ganglia circuitry in Parkinson's disease with freezing of gait.

OBJECTIVE: This study aimed to examine the structural alterations of the deep gray matter (DGM) in the basal ganglia circuitry of Parkinson's disease (PD) patients with freezing of gait (FOG) using quantitative susceptibility mapping (QSM) and neuromelanin-sensitive magnetic resonance imaging (NM-MRI). METHODS: Twenty-five (25) PD patients with FOG (PD-FOG), 22 PD patients without FOG (PD-nFOG), and 30 age- and sex-matched healthy controls (HCs) underwent 3-dimensional multi-echo gradient recalled echo and NM-MRI scanning. The mean volume and susceptibility of the DGM on QSM data and the relative contrast (NMRC-SNpc) and volume (NMvolume-SNpc) of the substantia nigra pars compacta on NM-MRI were analyzed among groups. A multiple linear regression analysis was performed to explore the associations of FOG severity with MRI measurements and disease stage. RESULTS: The PD-FOG group showed higher susceptibility in the bilateral caudal substantia nigra (SN) compared to the HC group. Both the PD-FOG and PD-nFOG groups showed lower volumes than the HC group in the bilateral caudate and putamen as determined from the QSM data. The NMvolume-SNpc on NM-MRI in the PD-FOG group was significantly lower than in the HC and PD-nFOG groups. Both the PD-FOG and PD-nFOG groups showed significantly decreased NMRC-SNpc. CONCLUSIONS: The PD-FOG patients showed abnormal neostriatum atrophy, increases in iron deposition in the SN, and lower NMvolume-SNpc. The structural alterations of the DGM in the basal ganglia circuits could lead to the abnormal output of the basal ganglia circuit to trigger the FOG in PD patients.

Dynamical and individualised approach of transcranial ultrasound neuromodulation effects in non-human primates.

Low-frequency transcranial ultrasound stimulation (TUS) allows to alter brain functioning with a high spatial resolution and to reach deep targets. However, the time-course of TUS effects remains largely unknown. We applied TUS on three brain targets for three different monkeys: the anterior medial prefrontal cortex, the supplementary motor area and the perigenual anterior cingulate cortex. For each, one resting-state fMRI was acquired between 30 and 150 min after TUS as well as one without stimulation (control). We captured seed-based brain connectivity changes dynamically and on an individual basis. We also assessed between individuals and between targets homogeneity and brain features that predicted TUS changes. We found that TUS prompts heterogenous functional connectivity alterations yet retain certain consistent changes; we identified 6 time-courses of changes including transient and long duration alterations; with a notable degree of accuracy we found that brain alterations could partially be predicted. Altogether, our results highlight that TUS induces heterogeneous functional connectivity alterations. On a more technical point, we also emphasize the need to consider brain changes over-time rather than just observed during a snapshot; to consider inter-individual variability since changes could be highly different from one individual to another.

Mapping dysfunctional circuits in the frontal cortex using deep brain stimulation.

Frontal circuits play a critical role in motor, cognitive and affective processing, and their dysfunction may result in a variety of brain disorders. However, exactly which frontal domains mediate which (dys)functions remains largely elusive. We studied 534 deep brain stimulation electrodes implanted to treat four different brain disorders. By analyzing which connections were modulated for optimal therapeutic response across these disorders, we segregated the frontal cortex into circuits that had become dysfunctional in each of them. Dysfunctional circuits were topographically arranged from occipital to frontal, ranging from interconnections with sensorimotor cortices in dystonia, the primary motor cortex in Tourette's syndrome, the supplementary motor area in Parkinson's disease, to ventromedial prefrontal and anterior cingulate cortices in obsessive-compulsive disorder. Our findings highlight the integration of deep brain stimulation with brain connectomics as a powerful tool to explore couplings between brain structure and functional impairments in the human brain.

Telemedicine in patients with obsessive-compulsive disorder after deep brain stimulation: a case series.

Background: Patients suffering from refractory obsessive-compulsive disorder (OCD) who have undergone deep brain stimulation (DBS) surgery require repeated in-person programming visits. These sessions could be labor-intensive and may not always be feasible, particularly when in-person hospital visits are restricted. Telemedicine is emerging as a potential supplementary tool for post-operative care. However, its reliability and feasibility still require further validation due to the unconventional methods of interaction. Methods: A study was conducted on three patients with refractory OCD who had undergone DBS. Most of their programming sessions were completed via a remote programming system. These patients were recruited and monitored for a year. Changes in their clinical symptoms were assessed using the Yale-Brown Obsessive-Compulsive Scale-Second Edition (Y-BOCS-II), the Hamilton Anxiety Scale-14 (HAMA), the Hamilton Depression Scale-17 (HAMD), and the Short Form 36 Health Survey Questionnaire (SF-36). The scores from these assessments were reported. Results: At the last follow-up, two out of three patients were identified as responders, with their Y-BOCS-II scores improving by more than 35% (P1: 51%, P3: 42%). These patients also experienced some mood benefits. All patients observed a decrease in travel expenses during the study period. No severe adverse events were reported throughout the study. Conclusion: The group of patients showed improvement in their OCD symptoms within a 1-year follow-up period after DBS surgery, without compromising safety or benefits. This suggests that telemedicine could be a valuable supplementary tool when in-person visits are limited.

Enhanced sensitivity of temperature and magnetic field sensor based on FPIs with Vernier effect.

A kind of temperature and magnetic field sensor using Fabry-Perot interferometers (FPIs) and Vernier effect to enhance sensitivity is proposed. The sensor structure involves filling the FP air cavities with polydimethylsiloxane (PDMS) and magnetic fluid (MF) to create the PDMS and MF cavities for temperature and magnetic field detection, respectively. The two cavities are reflective structures, which are interconnected in series through a fiber-optic circulator. Experimental data demonstrates that the Vernier effect effectively enhances the sensor sensitivity. The average temperature sensitivity of the sensor is 26765 pm/°C within the range of 35∼39.5°C. The magnetic field intensity sensitivity is obtained to be -2245 pm/mT within the range of 3∼11 mT. The sensitivities of the temperature and magnetic field using the Vernier effect are about five times larger than those of the corresponding single FP cavity counterparts.

Optimizing Deep Brain Stimulation in Essential Tremor: A Randomized Controlled Trial for Target Consideration.

BACKGROUND AND OBJECTIVES: The thalamic ventral intermediate nucleus (VIM) is a well-established target for deep brain stimulation (DBS) in the treatment of essential tremor (ET). Increasing data indicate that the posterior subthalamic area (PSA) may be superior, but high-level evidence is limited. We aimed at further comparing the intraindividual efficacy and side effect profile of PSA vs VIM DBS in ET. METHODS: In this randomized, double-blind, crossover trial, 4-contact DBS leads were bilaterally implanted with single-trajectory covering the VIM and PSA. Patients were randomized postsurgery to 2 groups, receiving VIM stimulation (4-7 months) and then PSA stimulation (8-11 months) or vice versa. The primary end point was the difference in improvement from baseline to the end of the VIM vs PSA DBS period in the total score of the Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS). RESULTS: Ten patients with medically refractory ET were enrolled, and 9 completed the study. The difference between reduction of FTM-TRS total score in the PSA vs VIM DBS period was -7.4 (95% CI: -28.5 to 13.7, P = .328). Clinical benefit was achieved at significantly lower stimulation intensity under PSA DBS. Furthermore, PSA DBS provided greater improvement in head tremor subscore of FTM-TRS (PSA vs VIM: -2.2, P = .020) and disease-specific quality of life (PSA vs VIM: -13.8, P = .046) and induced fewer speech (Dysphonia Severity Index score: P = .043; diadochokinetic rate: P = .007; VDI score: P = .005) and gait disturbances compared with VIM DBS. Seven patients remained with PSA DBS after the crossover phase. CONCLUSION: Our study confirms that PSA-DBS is comparable with VIM-DBS in suppressing tremors, superior in improving disease-specific quality of life, and possibly more effective in reducing head tremor.

A Causality-Aware Graph Convolutional Network Framework for Rigidity Assessment in Parkinsonians.

Rigidity is one of the common motor disorders in Parkinson's disease (PD), which lead to life quality deterioration. The widely-used rating-scale-based approach for rigidity assessment still depends on the availability of experienced neurologists and is limited by rating subjectivity. Given the recent successful applications of quantitative susceptibility mapping (QSM) in auxiliary PD diagnosis, automated assessment of PD rigidity can be essentially achieved through QSM analysis. However, a major challenge is the performance instability due to the confounding factors (e.g., noise and distribution shift) which conceal the truly-causal features. Therefore, we propose a causality-aware graph convolutional network (GCN) framework, where causal feature selection is combined with causal invariance to ensure that causality-informed model decisions are reached. Firstly, a GCN model that integrates causal feature selection is systematically constructed at three graph levels: node, structure, and representation. In this model, a causal diagram is learned to extract a subgraph with truly-causal information. Secondly, a non-causal perturbation strategy is developed along with an invariance constraint to ensure the stability of the assessment results under different distributions, and thus avoid spurious correlations caused by distribution shifts. The superiority of the proposed method is shown by extensive experiments and the clinical value is revealed by the direct relevance of selected brain regions to rigidity in PD. Besides, its extensibility is verified on other two tasks: PD bradykinesia and mental state for Alzheimer's disease. Overall, we provide a clinically-potential tool for automated and stable assessment of PD rigidity. Our source code will be available at https://github.com/SJTUBME-QianLab/Causality-Aware-Rigidity.

Use of Compressed Sensing Accelerated, Low-Velocity Encoded, Isotropic Resolution, Phase Contrast Magnetic Resonance Angiography for SEEG Electrode Implantation.

OBJECTIVE: We assessed the feasibility of using compressed sensing accelerated, low-velocity encoded, isotropic resolution phase contrast (CLIP) magnetic resonance angiography (MRA) for avascular trajectory planning of stereoelectroencephalography. METHODS: Ten healthy subjects (1 woman and 9 men; age, 33.6 ± 9.0 years) and 20 consecutive patients (12 female patients; age, 22 ± 13.6 years) were enrolled in the present study. The healthy subjects underwent CLIP-MRA, and 3 other phase contrast MRA protocols with conventional parallel imaging (PI) acceleration, including low resolution with twofold PI (PI2), high resolution (HR) with fivefold PI (PI5), and HR-PI2. The patients underwent CLIP-MRA and computed tomography angiography (CTA). The image qualities were evaluated. The numbers and locations of trajectory-vessel conflict detected using CLIP-MRA were noted. RESULTS: With similar scan durations, CLIP-MRA achieved higher spatial resolution compared with low resolution with PI2 and detected significantly more branches compared with HR-PI5. With the same spatial resolution, the signal/noise and contrast/noise ratios of CLIP-MRA were higher than those with HR-PI2 with a shorter scan duration. For the 12 adult patients (10 female patients; 28.8 ± 12.7 years), CLIP-MRA had better signal/noise and contrast/noise ratios than CTA. The trajectory had required modification for 14 of the 20 patients (70%), with a proportion of trajectory modification of 10.7% (23 of 215 electrodes). The middle meningeal artery, cortical vessel, and skull vessel were the main vessels with conflict (n = 11, n = 7, and n = 5, respectively). CONCLUSIONS: In the present study, CLIP-MRA provided a clear cortical vascular display noninvasively without intravascular contrast and radiation. The middle meningeal artery and diploic and emissary veins were the main conflict vessels and could be clearly displayed using CLIP-MRA but not CTA.

Impaired night-time mobility in patients with Parkinson's disease: a systematic review.

Impaired bed mobility (IBM) is a symptom characteristic of patients having difficulty intentionally moving their bodies during nighttime sleep. IBM is one of the most common nocturnal symptoms of Parkinson's disease (PD) and may lead to extreme pain and even death; it also increases the burden on the patients' caregivers. In this systematic review, we included 19 studies involving a total of 1,407 patients with PD to observe the causes, assessment methods, and treatment options for IBM. We conclude that the extent of IBM is positively correlated with the severity of symptoms such as disease duration, dyskinesia and decreased sleep quality in patients with PD, and the evidence implies that IBM may be able to serve as a prodromal feature in the development of PD. IBM probably results from low nocturnal dopamine concentrations, reduced function of the spinal tract, torque problems in the muscles, and aging. Therefore, treatment is mostly based on continuously increasing the patient's nocturnal dopamine concentration, while deep brain stimulation (DBS) also has a mitigating effect on IBM. Both scales and sensors are commonly used to measure the severity of IBM, the wearable device monitoring and scales being updated makes measurements easier and more accurate. The future of the advancement in this field lies in the use of more family-oriented devices (such as smart phones or watches and bracelets, etc.) to monitor IBM's symptoms and select the appropriate therapeutic treatment according to the severity of the symptoms to relieve patients' suffering.

Corrigendum: Fixed-life or rechargeable battery for deep brain stimulation: preference and satisfaction in Chinese patients with Parkinson's disease.

[This corrects the article DOI: 10.3389/fneur.2021.668322.].

Methadone maintenance treatment and impulsivity: premature responding.

INTRODUCTION: Previous research showed that methadone maintenance treatment (MMT) is linked to impulsivity, with higher impulsivity levels being associated with for example, increased drug use. One aspect of impulsivity, most commonly studied in rodent research, is premature responding, the failure to wait for a starting signal. Premature responding is of high translational significance since it predicts the development of addiction-like behaviors in rodents. METHODS: We assessed 45 MMT patients and 46 demographically matched (age, sex, education, and handedness) healthy volunteers (HVs) on premature responding alongside action and inhibition of instructed and intentional trials using the Intentional Hand Task (IHT). RESULTS: The results showed markedly enhanced premature responses in the MMT vs. the HV group, which correlated positively with methadone dosage in the MMT patients. Throughout the task, MMT patients were faster across all trial parts and less accurate in response to instructed trials compared to HVs. CONCLUSIONS: The increase in premature motor reactions during variable waiting periods alongside increased motion speed and lower accuracy might reflect a specific motor inhibition deficit in MMT, a subcomponent of impulsivity not previously assessed in MMT. Incorporating an experimentally defined measure of impulsivity, such as premature responding, into existing test batteries used by clinicians might enable more tailored treatments addressing the increased impulsivity levels and associated dysfunctional behaviors in MMT.

Phytoplankton Biological Pump Controls the Spatiotemporal Bioaccumulation and Trophic Transfer of Antibiotics in a Large Subtropical River.

The spatiotemporal bioaccumulation, trophic transfer of antibiotics, and regulation of the phytoplankton biological pump were quantitatively evaluated in the Pearl River, South China. The occurrence of antibiotics in organisms indicated a significant spatiotemporal trend associated with the life cycle of phytoplankton. Higher temporal bioaccumulation factors (BAFs) were found in phytoplankton at the bloom site, while lower BAFs of antibiotics in organisms could not be explained by phytoplankton biomass dilution but were attributed to the low bioavailability of antibiotics, which was highly associated with distribution coefficients (R2 = 0.480-0.595, p < 0.05). Such lower BAFs of antibiotics in phytoplankton at higher biomass sites hampered the entry of antibiotics into food webs, and trophic dilutions were subsequently observed for antibiotics except for ciprofloxacin (CFX) and sulfamerazine (SMZ) at sites with blooms in all seasons. Distribution of CFX, norfloxacin (NFX), and sulfapyridine (SPD) showed further significant positive relationships with the plasma protein fraction (R2 = 0.275-0.216, p < 0.05). Both mean BAFs and trophic magnification factors (TMFs) were significantly negatively correlated with phytoplankton biomass (R2 = 0.661-0.741, p < 0.05). This study highlights the importance of the biological pump in the regulation of spatiotemporal variations in bioaccumulation and trophic transfer of antibiotics in anthropogenic-impacted eutrophic rivers in subtropical regions.

In-line temperature-compensated vector magnetic field sensor with side-polished fiber.

A novel, to the best of our knowledge, vector magnetic field sensor with temperature compensation is proposed and investigated. The proposed sensor is realized by side polishing a multi-mode optical fiber and adopting the surface plasmon resonance (SPR) effect. The side-polished surface is coated with a magnetic fluid (MF) and polydimethylsiloxane (PDMS) successively along the fiber axis. The as-fabricated sensor can be used not only for magnetic field strength and direction sensing, but also for temperature detection. The achieved magnetic field intensity sensitivities are 1720 pm/mT (90° direction) and -710 pm/mT (0° direction), and the temperature sensitivity is -2070 pm/°C. On top of its temperature compensation ability, the easy fabrication and very high sensitivity of the proposed sensor are attractive features for vector magnetic field sensing applications.

COVID-19-related intrusive thoughts and associated ritualistic behaviors.

This study evaluated COVID-19-related intrusive thoughts and associated ritualistic behaviors (CITRB). From March to May 2020, 1,118 Chinese high school students, college students, psychiatric outpatients, and community members completed a survey assessing CITRB, generalized anxiety, depression, somatization, obsessive-compulsive symptoms, and pandemic-related disruptions. Overall, participants reported mild to moderate CITRB, although certain thoughts/behaviors were more frequently endorsed, such as repeatedly telling others to take precautions against COVID-19 and checking COVID-19-related news. Being male, younger, a health-care worker, or in isolation/quarantine was associated with CITRB severity in community members. Obsessive-compulsive symptom severity, depression, somatic symptoms, and anxiety were associated with CITRB severity, although only obsessive-compulsive symptoms were uniquely associated with CITRB. This study provided evidence for the construct of CITRB, which may help mental health providers identify the nature and sources of COVID-19-related distress for some individuals as well as serve as a framework for evaluating obsessive-compulsive symptoms specific to large-scale crises.

A Causality-Driven Graph Convolutional Network for Postural Abnormality Diagnosis in Parkinsonians.

Abnormal posture is a common movement disorder in the progress of Parkinson's disease (PD), and this abnormality can increase the risk of falls or even disabilities. The conventional assessment approach depends on the judgment of well-trained experts via canonical scales. However, this approach requires extensive clinical expertise and is highly subjective. Considering the potential of quantitative susceptibility mapping (QSM) in PD diagnosis, this study explored the QSM-based method for the automated classification between PD patients with and without postural abnormalities. Nevertheless, a major challenge is that unstable non-causal features typically lead to less reliable performance. Therefore, we propose a causality-driven graph-convolutional-network framework based on multi-instance learning, where performance stability is enhanced through the invariant prediction principle and causal interventions. Specifically, we adopt an intervention strategy that combines a non-causal intervenor with causal prediction. A stability constraint is proposed to ensure robust integrated prediction under different interventions. Moreover, an intra-class homogeneity constraint is enforced for each individually-learned causality scoring module to promote the extraction of group-level general features, and hence achieve a balance between subject-specific and group-level features. The proposed method demonstrated promising performance through extensive experiments on a real clinical dataset. Also, the features extracted by our method coincide with those reported in previous medical studies on PD posture abnormalities. In general, our work provides a clinically-valuable approach for automated, objective, and reliable diagnosis of postural abnormalities in Parkinsonians. Our source code is publicly available at https://github.com/SJTUBME-QianLab/CausalGCN-PDPA.