Quantitative Analysis of Rhodobacter sphaeroides Storage Organelles via Cryo-Electron Tomography and Light Microscopy.

Bacterial cytoplasmic organelles are diverse and serve many varied purposes. Here, we employed Rhodobacter sphaeroides to investigate the accumulation of carbon and inorganic phosphate in the storage organelles, polyhydroxybutyrate (PHB) and polyphosphate (PP), respectively. Using cryo-electron tomography (cryo-ET), these organelles were observed to increase in size and abundance when growth was arrested by chloramphenicol treatment. The accumulation of PHB and PP was quantified from three-dimensional (3D) segmentations in cryo-tomograms and the analysis of these 3D models. The quantification of PHB using both segmentation analysis and liquid chromatography and mass spectrometry (LCMS) each demonstrated an over 10- to 20-fold accumulation of PHB. The cytoplasmic location of PHB in cells was assessed with fluorescence light microscopy using a PhaP-mNeonGreen fusion-protein construct. The subcellular location and enumeration of these organelles were correlated by comparing the cryo-ET and fluorescence microscopy data. A potential link between PHB and PP localization and possible explanations for co-localization are discussed. Finally, the study of PHB and PP granules, and their accumulation, is discussed in the context of advancing fundamental knowledge about bacterial stress response, the study of renewable sources of bioplastics, and highly energetic compounds.

Differential Cognitive Effects of Unilateral Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease.

OBJECTIVE: The aim of this study was to investigate the cognitive effects of unilateral directional versus ring subthalamic nucleus deep brain stimulation (STN DBS) in patients with advanced Parkinson's disease. METHODS: We examined 31 participants who underwent unilateral STN DBS (left n = 17; right n = 14) as part of an National Institutes of Health (NIH)-sponsored randomized, double-blind, crossover study contrasting directional versus ring stimulation. All participants received unilateral DBS implants in the hemisphere more severely affected by motor parkinsonism. Measures of cognition included verbal fluency, auditory-verbal memory, and response inhibition. We used mixed linear models to contrast the effects of directional versus ring stimulation and implant hemisphere on longitudinal cognitive function. RESULTS: Crossover analyses showed no evidence for group-level changes in cognitive performance related to directional versus ring stimulation. Implant hemisphere, however, impacted cognition in several ways. Left STN participants had lower baseline verbal fluency than patients with right implants (t [20.66 = -2.50, p = 0.02]). Verbal fluency declined after left (p = 0.013) but increased after right STN DBS (p < 0.001), and response inhibition was faster following right STN DBS (p = 0.031). Regardless of hemisphere, delayed recall declined modestly over time versus baseline (p = 0.001), and immediate recall was unchanged. INTERPRETATION: Directional versus ring STN DBS did not differentially affect cognition. Similar to prior bilateral DBS studies, unilateral left stimulation worsened verbal fluency performance. In contrast, unilateral right STN surgery increased performance on verbal fluency and response inhibition tasks. Our findings raise the hypothesis that unilateral right STN DBS in selected patients with predominant right brain motor parkinsonism could mitigate declines in verbal fluency associated with the bilateral intervention. ANN NEUROL 2024;95:1205-1219.

Differential contribution of sensorimotor cortex and subthalamic nucleus to unimanual and bimanual hand movements.

Why does unilateral deep brain stimulation improve motor function bilaterally? To address this clinical observation, we collected parallel neural recordings from sensorimotor cortex (SMC) and the subthalamic nucleus (STN) during repetitive ipsilateral, contralateral, and bilateral hand movements in patients with Parkinson's disease. We used a cross-validated electrode-wise encoding model to map electromyography data to the neural signals. Electrodes in the STN encoded movement at a comparable level for both hands, whereas SMC electrodes displayed a strong contralateral bias. To examine representational overlap across the two hands, we trained the model with data from one condition (contralateral hand) and used the trained weights to predict neural activity for movements produced with the other hand (ipsilateral hand). Overall, between-hand generalization was poor, and this limitation was evident in both regions. A similar method was used to probe representational overlap across different task contexts (unimanual vs. bimanual). Task context was more important for the STN compared to the SMC indicating that neural activity in the STN showed greater divergence between the unimanual and bimanual conditions. These results indicate that SMC activity is strongly lateralized and relatively context-free, whereas the STN integrates contextual information with the ongoing behavior.

Differential cognitive effects of unilateral left and right subthalamic nucleus deep brain stimulation for Parkinson disease.

Objective: To investigate hemispheric effects of directional versus ring subthalamic nucleus (STN) deep brain stimulation (DBS) surgery on cognitive function in patients with advanced Parkinson's disease (PD). Methods: We examined 31 PD patients (Left STN n = 17; Right STN n = 14) who underwent unilateral subthalamic nucleus (STN) DBS as part of a NIH-sponsored randomized, cross-over, double-blind (ring vs directional) clinical trial. Outcome measures were tests of verbal fluency, auditory-verbal memory, and response inhibition. First, all participants were pooled together to study the effects of directional versus ring stimulation. Then, we stratified the groups by surgery hemisphere and studied the longitudinal changes in cognition post-unilateral STN DBS. Results: Relative to pre-DBS cognitive baseline performances, there were no group changes in cognition following unilateral DBS for either directional or ring stimulation. However, assessment of unilateral DBS by hemisphere revealed a different pattern. The left STN DBS group had lower verbal fluency than the right STN group (t(20.66 = -2.50, p = 0.02). Over a period of eight months post-DBS, verbal fluency declined in the left STN DBS group (p = 0.013) and improved in the right STN DBS group over time (p < .001). Similarly, response inhibition improved following right STN DBS (p = 0.031). Immediate recall did not significantly differ over time, nor was it affected by implant hemisphere, but delayed recall equivalently declined over time for both left and right STN DBS groups (left STN DBS p = 0.001, right STN DBS differ from left STN DBS p = 0.794). Conclusions: Directional and ring DBS did not differentially or adversely affect cognition over time. Regarding hemisphere effects, verbal fluency decline was observed in those who received left STN DBS, along with the left and right STN DBS declines in delayed memory. The left STN DBS verbal fluency decrement is consistent with prior bilateral DBS research, likely reflecting disruption of the basal-ganglia-thalamocortical network connecting STN and inferior frontal gyrus. Interestingly, we found an improvement in verbal fluency and response inhibition following right STN DBS. It is possible that unilateral STN DBS, particularly in the right hemisphere, may mitigate cognitive decline.

Efficacy of a Digital Personalized Elimination Diet for the Self-Management of Irritable Bowel Syndrome and Comorbid Irritable Bowel Syndrome and Inflammatory Bowel Disease.

INTRODUCTION: Most patients with irritable bowel syndrome (IBS) and dual-diagnosis IBS and inflammatory bowel disease (IBD) report that symptoms originate from or are exacerbated by trigger foods. Despite patient interest and need, there is no consensus on what diet is optimal. Popular diets have notable limitations including cost, length, implementation complexity, and lack of personalization. METHODS: This pilot study evaluated the feasibility, desirability, and effect on gastrointestinal symptoms of a digitally delivered personalized elimination diet for patients with IBS and comorbid IBS/IBD, powered by machine learning. Participants were recruited online and were provided access to a digital personalized nutrition tool for 9 weeks (N = 37; IBS only = 16, Crohn's disease and IBS = 9, and ulcerative colitis and IBS = 12). RESULTS: Significant symptom improvement was seen for 81% of participants at study midpoint and persisted for 70% at end point, measured by the relevant symptom severity score (IBS symptom severity score, Patient Simple Clinical Colitis Activity Index, or Mobile Health Index for Crohn's disease). Clinically significant symptom improvement was observed in 78% of participants at midpoint and 62% at end point. Twenty-five participants (67.6%) achieved total symptomatic resolution by the end of study. Patient-reported quality of life improved for 89% of participants. Ninety-five percentage daily engagement, 95% retention, 89% adherence and 92% satisfaction with the program were reported. DISCUSSION: Dietary elimination can improve symptoms and quality of life in patients with IBS and comorbid IBS/IBD. Digital technology can personalize dietary interventions and improve adherence. Randomized controlled trials are warranted.

Multichannel magnetogastrogram: a clinical marker for pediatric chronic nausea.

Chronic nausea is a widespread functional disease in children with numerous comorbidities. High-resolution electrogastrogram (HR-EGG) has shown sufficient sensitivity as a noninvasive clinical marker to objectively detect distinct gastric slow wave properties in children with functional nausea. We hypothesized that the increased precision of magnetogastrogram (MGG) slow wave recordings could provide supplementary information not evident on HR-EGG. We evaluated simultaneous pre- and postprandial MGG and HR-EGG recordings in pediatric patients with chronic nausea and healthy asymptomatic subjects, while also measuring nausea intensity and nausea severity. We found significant reductions in postprandial dominant frequency and normogastric power, and higher levels of postprandial bradygastric power in patients with nausea in both MGG and HR-EGG. MGG also detected significantly lower preprandial normogastric power in patients. A significant difference in the mean preprandial gastric slow wave propagation direction was observed in patients as compared with controls in both MGG (control: 180 ± 61°, patient: 34 ±72°; P < 0.05) and HR-EGG (control: 240 ± 39°, patient: 180 ± 46°; P < 0.05). Patients also showed a significant change in the mean slow wave direction between pre- and postprandial periods in MGG (P < 0.05). No statistical differences were observed in propagation speed between healthy subjects and patients in either MGG or HR-EGG pre/postprandial periods. The use of MGG and/or HR-EGG represents an opportunity to assess noninvasively the effects of chronic nausea on gastric slow wave activity. MGG data may offer the opportunity for further refinement of the more portable and economical HR-EGG in future machine-learning approaches for functional nausea.NEW & NOTEWORTHY Pediatric chronic nausea is a difficult-to-measure subjective complaint that requires objective diagnosis, clinical assessment, and individualized treatment plans. Our study demonstrates that multichannel MGG used in conjunction with custom HR-EGG detects key pathological signatures of functional nausea in children. This quantifiable measure may allow more personalized diagnosis and treatment in addition to minimizing the cost and potential radiation associated with current diagnostic approaches.

Belief or disbelief in feedback influences the detection efficiency of the feedback concealed information test.

The feedback concealed information test (fCIT) is a new variant of the CIT that added feedback about participants' concealing performances in the classical CIT. The advantage of the fCIT is that the resulting feedback related event-related potentials (ERPs) can be used to detect concealed information. However, the detection efficiency of feedback-based ERPs varies across studies. The present experiment examined whether the extent participants believed the feedback influenced their detection efficiency. Specifically, participants did a mock crime and were then tested in a fCIT. Following the fCIT, participants were asked to report how much they believed the feedback was accurate. Results showed that there were no significant correlations between the amplitude of the feedback related negativity (FRN), feedback P300, and participants' self-report at the group level. However, individual analyses showed that the detection efficiency of both the FRN and feedback P300 were influenced by participants' belief about the presented feedback. The detection efficiency of the FRN and the feedback P300 was higher among participants who believed the feedback. These findings suggest that the fCIT is dependent to some extent on the participants' level of belief in the feedback.

Local anatomy, stimulation site, and time alter directional deep brain stimulation impedances.

Directional deep brain stimulation (DBS) contacts provide greater spatial flexibility for therapy than traditional ring-shaped electrodes, but little is known about longitudinal changes of impedance and orientation. We measured monopolar and bipolar impedance of DBS contacts in 31 patients who underwent unilateral subthalamic nucleus deep brain stimulation as part of a randomized study (SUNDIAL, NCT03353688). At different follow-up visits, patients were assigned new stimulation configurations and impedance was measured. Additionally, we measured the orientation of the directional lead during surgery, immediately after surgery, and 1 year later. Here we contrast impedances in directional versus ring contacts with respect to local anatomy, active stimulation contact(s), and over time. Directional contacts display larger impedances than ring contacts. Impedances generally increase slightly over the first year of therapy, save for a transient decrease immediately post-surgery under general anesthesia during pulse generator placement. Local impedances decrease at active stimulation sites, and contacts in closest proximity to internal capsule display higher impedances than other anatomic sites. DBS leads rotate slightly in the immediate postoperative period (typically less than the angle of a single contact) but otherwise remain stable over the following year. These data provide useful information for setting clinical stimulation parameters over time.

Cortical and Subthalamic Nucleus Spectral Changes During Limb Movements in Parkinson's Disease Patients with and Without Dystonia.

BACKGROUND: Dystonia is an understudied motor feature of Parkinson's disease (PD). Although considerable efforts have focused on brain oscillations related to the cardinal symptoms of PD, whether dystonia is associated with specific electrophysiological features is unclear. OBJECTIVE: The objective of this study was to investigate subcortical and cortical field potentials at rest and during contralateral hand and foot movements in patients with PD with and without dystonia. METHODS: We examined the prevalence and distribution of dystonia in patients with PD undergoing deep brain stimulation surgery.  During surgery, we recorded intracranial electrophysiology from the motor cortex and directional electrodes in the subthalamic nucleus (STN) both at rest and during self-paced repetitive contralateral hand and foot movements. Wavelet transforms and mixed models characterized changes in spectral content in patients with and without dystonia. RESULTS: Dystonia was highly prevalent at enrollment (61%) and occurred most commonly in the foot. Regardless of dystonia status, cortical recordings display beta (13-30 Hz) desynchronization during movements versus rest, while STN signals show increased power in low frequencies (6.0 ± 3.3 and 4.2 ± 2.9 Hz peak frequencies for hand and foot movements, respectively). Patients with PD with dystonia during deep brain stimulation surgery displayed greater M1 beta power at rest and STN low-frequency power during movements versus those without dystonia. CONCLUSIONS: Spectral power in motor cortex and STN field potentials differs markedly during repetitive limb movements, with cortical beta desynchronization and subcortical low-frequency synchronization, especially in patients with PD with dystonia. Greater knowledge on field potential dynamics in human motor circuits can inform dystonia pathophysiology in PD and guide novel approaches to therapy. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

A novel and effective item-source complex trial protocol: Discrimination of guilty from both knowledgeable and unknowledgeable innocent subjects.

Innocent subjects who are knowledgeable of crime-related information will often be misclassified as "guilty" in P300-based complex trial protocol (CTP). Therefore, it is necessary to develop a more rigorous CTP that can effectively discriminate the guilty from both the knowledgeable and the unknowledgeable innocents. Sometimes the guilty and the knowledgeable innocents possess the same item memories but different source memories. The present study designed a novel item-source complex trial protocol based on the differences of source memory among the three kinds of individuals. Either the crime-related probe (e.g., the stolen ring) or one of the crime-unrelated stimuli (e.g., watch, earring, bracelet, or bangle) (item memory) was presented in the first part of each trail, and either a stealing-source word (e.g., stole) or other-source word (e.g., fetched) (source memory) was presented in the second part of each trail. The results showed that: (1) the P300 evoked by item memory could effectively discriminated the guilty from the unknowledgeable innocent (AUC = 0.76) but failed to effectively discriminate the guilty from the knowledgeable innocent (AUC = 0.60); (2) the late positive component evoked by source memory could effectively discriminated the guilty from both the knowledgeable innocent (AUC = 0.94) and the unknowledgeable innocent (AUC = 0.84) in one test.

The effects of practicing a novel countermeasure on both the semantic and episodic memory-based complex trial protocols.

This study applied a countermeasure-resistant version of the Concealed Information Test - the Complex Trial Protocol (CTP) - in an information recognition scenario. We replicated and extended the effects of a novel countermeasure developed by Lukács et al., (2016) on both Semantic and Episodic CTPs. We measured participants' response time and P300 event-related potential to rare, crime-relevant probe stimuli, or frequent, non-crime-relevant irrelevant stimuli in two ways: 1) probe vs the average of all irrelevants (PvIall), and 2) probe vs the maximum irrelevant (PvImax). We hypothesized that countermeasure use would only impair information recognition (as indexed by P300) when participants had practiced the countermeasure beforehand. We further hypothesized that recognition of less salient, Episodic information (i.e., jewelry items from a mock crime) would be impaired by countermeasure use more than the recognition of highly salient, Semantic information (i.e., birthdates). Individual diagnostics based on the area under the receiver operating characteristic curve (Semantic CTP: practice n = 22, non-practice n = 23; Episodic CTP: practice n = 19, non-practice n = 18) revealed that the Semantic CTP was affected by the novel countermeasure, but both PvIall and PvImax analyses remained diagnostically useful. The Episodic CTP's performance, however, was reduced to chance, regardless of practice or analysis type. These results are important for both the field of deception detection and the CTP literature. Research on improvements to the Episodic CTP is required.

Automated Machine Learning Pipeline Framework for Classification of Pediatric Functional Nausea Using High-Resolution Electrogastrogram.

OBJECTIVE: Pediatric functional nausea is challenging for patients to manage and for clinicians to treat since it lacks objective diagnosis and assessment. A data-driven non-invasive diagnostic screening tool that distinguishes the electro-pathophysiology of pediatric functional nausea from healthy controls would be an invaluable aid to support clinical decision-making in diagnosis and management of patient treatment methodology. The purpose of this paper is to present an innovative approach for objectively classifying pediatric functional nausea using cutaneous high-resolution electrogastrogram data. METHODS: We present an Automated Electrogastrogram Data Analytics Pipeline framework and demonstrate its use in a 3x8 factorial design to identify an optimal classification model according to a defined objective function. Low-fidelity synthetic high-resolution electrogastrogram data were generated to validate outputs and determine SOBI-ICA noise reduction effectiveness. RESULTS: A 10 parameter support vector machine binary classifier with a radial basis function kernel was selected as the overall top-performing model from a pool of over 1000 alternatives via maximization of an objective function. This resulted in a 91.6% test ROC AUC score. CONCLUSION: Using an automated machine learning pipeline approach to process high-resolution electrogastrogram data allows for clinically significant objective classification of pediatric functional nausea. SIGNIFICANCE: To our knowledge, this is the first study to demonstrate clinically significant performance in the objective classification of pediatric nausea patients from healthy control subjects using experimental high-resolution electrogastrogram data. These results indicate a promising potential for high-resolution electrogastrography to serve as a data-driven screening tool for the objective diagnosis of pediatric functional nausea.

Bayesian Data Analysis: A Fresh Approach to Power Issues and Null Hypothesis Interpretation.

One of the first things one learns in a basic psychology or statistics course is that you cannot prove the null hypothesis that there is no difference between two conditions such as a patient group and a normal control group. This remains true. However now, thanks to ongoing progress by a special group of devoted methodologists, even when the result of an inferential test is p > .05, it is now possible to rigorously and quantitatively conclude that (a) the null hypothesis is actually unlikely, and (b) that the alternative hypothesis of an actual difference between treatment and control is more probable than the null. Alternatively, it is also possible to conclude quantitatively that the null hypothesis is much more likely than the alternative. Without Bayesian statistics, we couldn't say anything if a simple inferential analysis like a t-test yielded p > .05. The present, mostly non-quantitative article describes free resources and illustrative procedures for doing Bayesian analysis, with t-test and ANOVA examples.

The effect of chronic nausea on gastric slow wave spatiotemporal dynamics in children.

BACKGROUND: Chronic nausea in adolescents with functional gastrointestinal disorders is an increasingly reported but poorly understood symptom that negatively affects quality of life. Functional gastrointestinal disorders are known to correlate closely with slow wave rhythm disturbances. The ability to characterize gastric electrophysiologic perturbations in functional nausea patients could provide potential diagnostic and therapeutic tools for nausea patients. METHODS: We used high-resolution electrogastrograms (HR-EGG) to measure gastric slow wave parameters in pediatric chronic nausea patients and healthy subjects both pre- and postprandial. We computed the dominant frequency, percentage power distribution, gastric slow wave propagation direction, and speed from HR-EGG. KEY RESULTS: We observed significant differences in the dominant frequency and power distributed in normal and bradyarrhythmia frequency ranges when comparing patients and healthy subjects. Propagation patterns in healthy subjects were predominantly anterograde, while patients exhibited a variety of abnormalities including retrograde, anterograde, and disrupted patterns. There was a significant difference in the preprandial mean slow wave direction between healthy subjects (222° ± 22°) and patients (103° ± 66°; p Ë‚ 0.01), although the postprandial mean direction between healthy subjects and patients was similar (p = 0.73). No significant difference in slow wave propagation speed was found between patients and healthy subjects in either pre- (p = 0.21) or postprandial periods (p = 0.75). CONCLUSIONS AND INFERENCES: The spatiotemporal characterization of gastric slow wave activity using HR-EGG distinguishes symptomatic chronic nausea patients from healthy subjects. This characterization may in turn inform and direct clinical decision-making and lead to further insight into its pathophysiology.

Familiarity-related filler items enhance the RT CIT, but not the P300 CIT: Episodic vs. Semantic memory protocols.

The reaction time-based concealed information test (RT CIT) typically uses three types of stimuli: 1) probe (i.e., crime-related item), 2) irrelevant (i.e., crime-unrelated item) and 3) target (i.e., an irrelevant item assigned a unique response so as to ensure attention to the test). Lukács, et al., (2017) introduced familiarity-related filler items to the RT CIT, enhancing the efficacy of the test for both single and multiple probe (per block) protocols. Our study aims to A) replicate the effects of familiarity-related filler items on the RT CIT, B) use P300 to investigate the mechanisms of the fillers-related enhancement effect on the RT CIT, C) investigate whether these fillers can enhance the efficacy of the typical P300-based CIT, and D) explore the effects of fillers on the semantic and episodic versions of the P300 and RT CITs. We replicated a clear fillers-related enhancement of the RT CIT (N = 38 for Fillers, N = 37 for No Fillers). Semantic and Episodic experiments were enhanced equally-well by filler items. No effect of fillers was observed on P300 amplitude for CIT stimuli, however, an interaction involving P300 latency suggests that fillers facilitated the processing of Semantic information over Episodic information. Our study independently replicates a valuable improvement of the traditional RT CIT, investigates the potential mechanisms of this enhancement effect, and demonstrates important differences between the P300 and RT CITs.

Optimization of fused filament fabrication process parameters under uncertainty to maximize part geometry accuracy.

This work presents a novel process design optimization framework for additive manufacturing (AM) by integrating physics-informed computational simulation models with experimental observations. The proposed framework is implemented to optimize the process parameters such as extrusion temperature, extrusion velocity, and layer thickness in the fused filament fabrication (FFF) AM process, in order to reduce the variability in the geometry of the manufactured part. A coupled thermo-mechanical model is first developed to simulate the FFF process. The temperature history obtained from the heat transfer analysis is then used as input for the mechanical deformation analysis to predict the dimensional inaccuracy of the additively manufactured part. The simulation model is then corrected based on experimental observations through Bayesian calibration of the model discrepancy to make it more accurately represent the actual manufacturing process. Based on the corrected prediction model, a robustness-based design optimization problem is formulated to optimize the process parameters, while accounting for multiple sources of uncertainty in the manufacturing process, process models, and measurements. Physical experiments are conducted to verify the effectiveness of the proposed optimization framework.

Deleterious effects of probe-related versus irrelevant targets on the "CIT effect" in the P300- and RT-based three-stimulus protocol for detection of concealed information.

Two groups of participants committed the same mock crime in which one of two items, a watch or a ring, was removed from a drawer and concealed. One group, the crime-familiar group next experienced a three-stimulus protocol (3SP), a Concealed Information Test (CIT), in which they were tested on the stolen (probe) item presented in a random series of five irrelevant (unseen) stimuli from the same jewelry category. A left-hand button press, meaning "I don't recognize" was to follow each of these six items. A right-hand press ("I do recognize") was to follow the one other presented item, the target item, which in the case of the crime-familiar group was the other, not-stolen item in the drawer at the mock crime scene. For the other crime-unfamiliar group, the target was a sixth unseen irrelevant item as in the original P300 CIT. In terms of P300 latency and reaction time (RT), crime-familiar participants processed all stimuli faster than crime-unfamiliar participants. The CIT effects (probe-minus-irrelevant differences) for crime-familiar group members were inferior to those of crime-unfamiliar group members for RT and P300 amplitude measures. Thus, familiar targets negatively impact the 3SP.