N2GNet tracks gait performance from subthalamic neural signals in Parkinson's disease.

Adaptive deep brain stimulation (DBS) provides individualized therapy for people with Parkinson's disease (PWP) by adjusting the stimulation in real-time using neural signals that reflect their motor state. Current algorithms, however, utilize condensed and manually selected neural features which may result in a less robust and biased therapy. In this study, we propose Neural-to-Gait Neural network (N2GNet), a novel deep learning-based regression model capable of tracking real-time gait performance from subthalamic nucleus local field potentials (STN LFPs).

N2GNet tracks gait performance from subthalamic neural signals in Parkinson's disease.

Adaptive deep brain stimulation (DBS) provides individualized therapy for people with Parkinson's disease (PWP) by adjusting the stimulation in real-time using neural signals that reflect their motor state. Current algorithms, however, utilize condensed and manually selected neural features which may result in a less robust and biased therapy. In this study, we propose Neural-to-Gait Neural network (N2GNet), a novel deep learning-based regression model capable of tracking real-time gait performance from subthalamic nucleus local field potentials (STN LFPs).

Lateral thinking: Neurodegeneration of the cortical cholinergic system in Alzheimer's disease.

Introduction: Atrophy of the nucleus basalis of Meynert (NBM) is an early indicator of Alzheimer's disease (AD). However, reduced integrity of the NBM white matter tracts may be more relevant for cognitive impairment and progression to dementia than NBM volume. Research is needed to compare differences in NBM volume and integrity of the lateral and medial NBM tracts across early and later stages of AD progression.

The digital signature of emergent tremor in Parkinson's disease.

Emergent tremor in Parkinson's disease (PD) can occur during sustained postures or movements that are different from action tremor. Tremor can contaminate the clinical rating of bradykinesia during finger tapping. Currently, there is no reliable way of isolating emergent tremor and measuring the cardinal motor symptoms based on voluntary movements only.

Lateral Thinking: Pathway Specific Neurodegeneration of the Cortical Cholinergic System in Alzheimer's Disease.

Introduction: Atrophy of the nucleus basalis of Meynert (NBM) is an early indicator of Alzheimer's disease (AD). However, reduced integrity of the NBM white matter tracts may be more relevant for cognitive impairment and progression to dementia than NBM volume. Research is needed to compare differences in NBM volume and integrity of the lateral and medial NBM tracts across early and later stages of AD progression.

Comprehensive real time remote monitoring for Parkinson's disease using Quantitative DigitoGraphy.

People with Parkinson's disease (PWP) face critical challenges, including lack of access to neurological care, inadequate measurement and communication of motor symptoms, and suboptimal medication management and compliance. We have developed QDG-Care: a comprehensive connected care platform for Parkinson's disease (PD) that delivers validated, quantitative metrics of all motor signs in PD in real time, monitors the effects of adjusting therapy and medication adherence and is accessible in the electronic health record. In this article, we describe the design and engineering of all components of QDG-Care, including the development and utility of the QDG Mobility and Tremor Severity Scores.

A novel reporter for helicase activity in translation uncovers DDX3X interactions.

DDX3X regulates the translation of a subset of human transcripts containing complex 5' untranslated regions (5' UTRs). In this study, we developed the helicase activity reporter for translation (HART), which uses DDX3X-sensitive 5' UTRs to measure DDX3X-mediated translational activity in cells. To directly measure RNA structure in DDX3X-dependent mRNAs, we used SHAPE-MaP to determine the secondary structures present in DDX3X-sensitive 5' UTRs and then used HART to investigate how sequence alterations influence DDX3X sensitivity.

Proceedings of the 11th Annual Deep Brain Stimulation Think Tank: pushing the forefront of neuromodulation with functional network mapping, biomarkers for adaptive DBS, bioethical dilemmas, AI-guided neuromodulation, and translational advancements.

The Deep Brain Stimulation (DBS) Think Tank XI was held on August 9-11, 2023 in Gainesville, Florida with the theme of "Pushing the Forefront of Neuromodulation". The keynote speaker was Dr. Nico Dosenbach from Washington University in St.

Quantitative DigitoGraphy: a Comprehensive Real-Time Remote Monitoring System for Parkinson's Disease.

People with Parkinson's disease (PWP) face critical challenges, including lack of access to neurological care, inadequate measurement and communication of motor symptoms, and suboptimal medication management and compliance. We have developed QDG-Care: a comprehensive connected care platform for Parkinson's disease (PD) that delivers validated, quantitative metrics of all motor signs in PD in real time, monitors the effects of adjusting therapy and medication adherence and is accessible in the electronic health record. In this article, we describe the design and engineering of all components of QDG-Care, including the development and utility of the QDG Mobility and Tremor Severity Scores.

Unraveling the complexities of programming neural adaptive deep brain stimulation in Parkinson's disease.

Over the past three decades, deep brain stimulation (DBS) for Parkinson's disease (PD) has been applied in a continuous open loop fashion, unresponsive to changes in a given patient's state or symptoms over the course of a day. Advances in recent neurostimulator technology enable the possibility for closed loop adaptive DBS (aDBS) for PD as a treatment option in the near future in which stimulation adjusts in a demand-based manner. Although aDBS offers great clinical potential for treatment of motor symptoms, it also brings with it the need for better understanding how to implement it in order to maximize its benefits.

The digital signature of emergent tremor in Parkinson's disease.

Background: Emergent tremor in Parkinson's disease (PD) can occur during sustained postures or movement that is different from action tremor. Tremor can contaminate the clinical rating of bradykinesia during finger tapping. Currently, there is no reliable way of isolating emergent tremor and measuring the cardinal motor symptoms based on voluntary movements only.

Determinants of DDX3X sensitivity uncovered using a helicase activity in translation reporter.

DDX3X regulates the translation of a subset of human transcripts containing complex 5' untranslated regions (5' UTRs). In this study we developed the helicase activity reporter for translation (HART) which uses DDX3X-sensitive 5' UTRs to measure DDX3X mediated translational activity in cells. To dissect the structural underpinnings of DDX3X dependent translation, we first used SHAPE-MaP to determine the secondary structures present in DDX3X-sensitive 5' UTRs and then employed HART to investigate how their perturbation impacts DDX3X-sensitivity.

An Individualized Tractography Pipeline for the Nucleus Basalis of Meynert Lateral Tract.

Background: At the center of the cortical cholinergic network, the nucleus basalis of Meynert (NBM) is crucial for the cognitive domains most vulnerable in PD. Preclinical evidence has demonstrated the positive impact of NBM deep brain stimulation (DBS) on cognition but early human trials have had mixed results. It is possible that DBS of the lateral NBM efferent white matter fiber bundle may be more effective at improving cognitive-motor function.

No laughing white matter: Reduced integrity of the cortical cholinergic pathways in Parkinson's disease-related cognitive impairment.

Background: Approximately one third of recently diagnosed Parkinson's disease (PD) patients experience cognitive decline. The nucleus basalis of Meynert (NBM) degenerates early in PD and is crucial for cognitive function. The two main NBM white matter pathways include a lateral and medial trajectory.

No Laughing White Matter: Cortical Cholinergic Pathways and Cognitive Decline in Parkinson's Disease.

Background: Approximately one third of recently diagnosed Parkinson's disease (PD) patients experience cognitive decline. The nucleus basalis of Meynert (NBM) degenerates early in PD and is crucial for cognitive function. The two main NBM white matter pathways include a lateral and medial trajectory.

The Sequence Effect Worsens Over Time in Parkinson's Disease and Responds to Open and Closed-Loop Subthalamic Nucleus Deep Brain Stimulation.

Background: The sequence effect is the progressive deterioration in speech, limb movement, and gait that leads to an inability to communicate, manipulate objects, or walk without freezing of gait. Many studies have demonstrated a lack of improvement of the sequence effect from dopaminergic medication, however few studies have studied the metric over time or investigated the effect of open-loop deep brain stimulation in people with Parkinson's disease (PD).

Objective: To investigate whether the sequence effect worsens over time and/or is improved on clinical (open-loop) deep brain stimulation (DBS).

Bradykinesia and Its Progression Are Related to Interhemispheric Beta Coherence.

Objective: Bradykinesia is the major cardinal motor sign of Parkinson disease (PD), but its neural underpinnings are unclear. The goal of this study was to examine whether changes in bradykinesia following long-term subthalamic nucleus (STN) deep brain stimulation (DBS) are linked to local STN beta (13-30 Hz) dynamics or a wider bilateral network dysfunction.

Methods: Twenty-one individuals with PD implanted with sensing neurostimulators (Activa® PC + S, Medtronic, PLC) in the STN participated in a longitudinal 'washout' therapy study every three to 6 months for an average of 3 years.

Lysate and cell-based assays to probe the translational role of RNA helicases.

Translation initiation is the first step in protein synthesis, during which the small subunit of the ribosome scans the 5' untranslated region (5'UTR) of an mRNA to identify a start codon and commence translation elongation. By unwinding and modulating secondary structures and other RNA features present in the 5'UTR, RNA helicases can regulate ribosome scanning and start codon selection. This chapter presents an approach to measure the effect of RNA helicases on mRNA translation initiation.

Quantitative Digitography Measures Motor Symptoms and Disease Progression in Parkinson's Disease.

Background: Assessment of motor signs in Parkinson's disease (PD) requires an in-person examination. However, 50% of people with PD do not have access to a neurologist. Wearable sensors can provide remote measures of some motor signs but require continuous monitoring for several days.

Ramp Rate Evaluation and Configuration for Safe and Tolerable Closed-Loop Deep Brain Stimulation.

Closed-loop deep brain stimulation is a novel form of therapy that has shown benefit in preliminary studies and may be clinically available in the near future. Initial closed-loop studies have primarily focused on responding to sensed biomarkers with adjustments to stimulation amplitude, which is often perceptible to study participants depending on the slew or "ramp" rate of the amplitude changes. These subjective responses to stimulation ramping can result in transient side effects, illustrating that ramp rate is a unique safety parameter for closed-loop neural systems.

Differential Effects of Pathological Beta Burst Dynamics Between Parkinson's Disease Phenotypes Across Different Movements.

Resting state beta band (13-30 Hz) oscillations represent pathological neural activity in Parkinson's disease (PD). It is unknown how the peak frequency or dynamics of beta oscillations may change among fine, limb, and axial movements and different disease phenotypes. This will be critical for the development of personalized closed loop deep brain stimulation (DBS) algorithms during different activity states.

Lack of progression of beta dynamics after long-term subthalamic neurostimulation.

Objective: To investigate the progression of neural and motor features of Parkinson's disease in a longitudinal study, after washout of medication and bilateral subthalamic nucleus deep brain stimulation (STN DBS).

Methods: Participants with clinically established Parkinson's disease underwent bilateral implantation of DBS leads (18 participants, 13 male) within the STN using standard functional frameless stereotactic technique and multi-pass microelectrode recording. Both DBS leads were connected to an implanted investigative sensing neurostimulator (Activa™ PC + S, Medtronic, PLC).

DDX3X and DDX3Y are redundant in protein synthesis.

DDX3 is a DEAD-box RNA helicase that regulates translation and is encoded by the X- and Y-linked paralogs and While DDX3X is ubiquitously expressed in human tissues and essential for viability, DDX3Y is male-specific and shows lower and more variable expression than DDX3X in somatic tissues. Heterozygous genetic lesions in mediate a class of developmental disorders called DDX3X syndrome, while loss of is implicated in male infertility. One possible explanation for female-bias in DDX3X syndrome is that encodes a polypeptide with different biochemical activity.