Nothing Special   »   [go: up one dir, main page]

You seem to have javascript disabled. Please note that many of the page functionalities won't work as expected without javascript enabled.
 
 
Sign in to use this feature.

Years

Between: -

Subjects

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Journals

Article Types

Countries / Regions

Search Results (30)

Search Parameters:
Keywords = physiological tremor

Order results
Result details
Results per page
Select all
Export citation of selected articles as:
9 pages, 358 KiB  
Article
A Novel GBF1 Variant in a Charcot-Marie-Tooth Type 2: Insights from Familial Analysis
by Valentina Ciampana, Lucia Corrado, Luca Magistrelli, Elena Contaldi, Cristoforo Comi, Sandra D’Alfonso and Domizia Vecchio
Genes 2024, 15(12), 1556; https://doi.org/10.3390/genes15121556 (registering DOI) - 29 Nov 2024
Viewed by 186
Abstract
Background/Objectives: Axonal Charcot–Marie–Tooth disease type 2 (CMT2) accounts for 24% of Hereditary Motor/Sensory Peripheral Neuropathies. CMT2 type GG, due to four distinct heterozygous mutations in the Golgi brefeldin A resistant guanine nucleotide exchange factor 1 (GBF1) gene (OMIM 606483), was described [...] Read more.
Background/Objectives: Axonal Charcot–Marie–Tooth disease type 2 (CMT2) accounts for 24% of Hereditary Motor/Sensory Peripheral Neuropathies. CMT2 type GG, due to four distinct heterozygous mutations in the Golgi brefeldin A resistant guanine nucleotide exchange factor 1 (GBF1) gene (OMIM 606483), was described in seven cases from four unrelated families with autosomal dominant inheritance. It is characterized by slowly progressive distal muscle weakness and atrophy, primarily affecting the lower limbs. Here, we present two siblings sharing a novel GBF1 variant. Methods: Patient II.1 (male, 61 years at onset) presented lower limb hypoesthesia and walking difficulty; the examination revealed a postural tremor, a positive Romberg test, and muscle atrophy in the lower limbs and hands. Patient II.2 (his sister, 59 years at onset) had lower limb dysesthesias, hand paresthesia, and lower-limb stiffness. They underwent clinical evaluations, blood tests, and electroneurography. Their father represents a potentially affected individual, although a genetic analysis was not conducted. Results: All tests for peripheral neuropathies were unremarkable, including metabolic and autoimmune screening. Both showed a mixed demyelinating–axonal sensory–motor neuropathy. Genetic analysis revealed a new heterozygous GBF1 variant of uncertain significance. Conclusions: Based on autosomal dominant inheritance, as well as clinical and physiological features, a possible novel CMT2GG was diagnosed. Further research, including functional assays and in vitro studies, is necessary to confirm this variant’s causal link. Full article
Show Figures

Figure 1

Figure 1
<p>Pedigree of the family. The black-filled symbols represent symptomatic individuals for whom the genetic analysis supported the diagnosis, while the gray-filled symbol represents a potentially affected individual where a genetic analysis was not conducted.</p>
Full article ">
20 pages, 8922 KiB  
Article
Prediction and Elimination of Physiological Tremor During Control of Teleoperated Robot Based on Deep Learning
by Juntao Chen, Zhiqing Zhang, Wei Guan, Xinxin Cao and Ke Liang
Sensors 2024, 24(22), 7359; https://doi.org/10.3390/s24227359 - 18 Nov 2024
Viewed by 416
Abstract
Currently, teleoperated robots, with the operator’s input, can fully perceive unknown factors in a complex environment and have strong environmental interaction and perception abilities. However, physiological tremors in the human hand can seriously affect the accuracy of processes that require high-precision control. Therefore, [...] Read more.
Currently, teleoperated robots, with the operator’s input, can fully perceive unknown factors in a complex environment and have strong environmental interaction and perception abilities. However, physiological tremors in the human hand can seriously affect the accuracy of processes that require high-precision control. Therefore, this paper proposes an EEMD-IWOA-LSTM model, which can decompose the physiological tremor of the hand into several intrinsic modal components (IMF) by using the EEMD decomposition strategy and convert the complex nonlinear and non-stationary physiological tremor curve of the human hand into multiple simple sequences. An LSTM neural network is used to build a prediction model for each (IMF) component, and an IWOA is proposed to optimize the model, thereby improving the prediction accuracy of the physiological tremor and eliminating it. At the same time, the prediction results of this model are compared with those of different models, and the results of EEMD-IWOA-LSTM presented in this study show obvious superior performance. In the two examples, the MSE of the prediction model proposed are 0.1148 and 0.00623, respectively. The defibrillation model proposed in this study can effectively eliminate the physiological tremor of the human hand during teleoperation and improve the control accuracy of the robot during teleoperation. Full article
(This article belongs to the Special Issue Advanced Robotic Manipulators and Control Applications)
Show Figures

Figure 1

Figure 1
<p>Control flow chart of teleoperation system.</p>
Full article ">Figure 2
<p>Tremor Suppression Model.</p>
Full article ">Figure 3
<p>LSTM structure diagram.</p>
Full article ">Figure 4
<p>Decomposition process of EEMD.</p>
Full article ">Figure 5
<p>EEMD-LSTM model structure diagram.</p>
Full article ">Figure 6
<p>IWOA flow chart.</p>
Full article ">Figure 7
<p>Decomposition results of EEMD.</p>
Full article ">Figure 8
<p>Modeling process in Example 1.</p>
Full article ">Figure 9
<p>Prediction results of tremor signal.</p>
Full article ">Figure 9 Cont.
<p>Prediction results of tremor signal.</p>
Full article ">Figure 10
<p>Fitness curve of each IMF component.</p>
Full article ">Figure 11
<p>Box diagram of different axes. (<b>a</b>) is the <span class="html-italic">x</span> axis, (<b>b</b>) is the <span class="html-italic">y</span> axis, and (<b>c</b>) is the <span class="html-italic">z</span> axis.</p>
Full article ">Figure 12
<p>Comparison of the effects of different activation functions.</p>
Full article ">Figure 13
<p>Prediction results of tremor signal.</p>
Full article ">Figure 14
<p>Error box diagram; (<b>a</b>) is the <span class="html-italic">x</span> axis, (<b>b</b>) is the <span class="html-italic">y</span> axis, and (<b>c</b>) is the <span class="html-italic">z</span> axis.</p>
Full article ">Figure 15
<p>Tremor data <math display="inline"><semantics> <mrow> <msup> <mrow> <mi mathvariant="normal">R</mi> </mrow> <mrow> <mn>2</mn> </mrow> </msup> </mrow> </semantics></math> for three axes in two cases; (<b>a</b>) Case 1; (<b>b</b>) Case 2.</p>
Full article ">
21 pages, 4570 KiB  
Article
Levodopa Impairs Lysosomal Function in Sensory Neurons In Vitro
by Oyedele J. Olaoye, Asya Esin Aksoy, Santeri V. Hyytiäinen, Aia A. Narits and Miriam A. Hickey
Biology 2024, 13(11), 893; https://doi.org/10.3390/biology13110893 - 2 Nov 2024
Viewed by 707
Abstract
Parkinson’s disease (PD) is the second-most common neurodegenerative disease worldwide. Patients are diagnosed based upon movement disorders, including bradykinesia, tremor and stiffness of movement. However, non-motor signs, including constipation, rapid eye movement sleep behavior disorder, smell deficits and pain are well recognized. Peripheral [...] Read more.
Parkinson’s disease (PD) is the second-most common neurodegenerative disease worldwide. Patients are diagnosed based upon movement disorders, including bradykinesia, tremor and stiffness of movement. However, non-motor signs, including constipation, rapid eye movement sleep behavior disorder, smell deficits and pain are well recognized. Peripheral neuropathy is also increasingly recognized, as the vast majority of patients show reduced intraepidermal nerve fibers, and sensory nerve conduction and sensory function is also impaired. Many case studies in the literature show that high-dose levodopa may induce or exacerbate neuropathy in PD, which is thought to involve levodopa’s metabolism to homocysteine. Here, we treated primary cultures of dorsal root ganglia and a sensory neuronal cell line with levodopa to examine effects on cell morphology, mitochondrial content and physiology, and lysosomal function. High-dose levodopa reduced mitochondrial membrane potential. At concentrations observed in the patient, levodopa enhanced immunoreactivity to beta III tubulin. Critically, levodopa reduced lysosomal content and also reduced the proportion of lysosomes that were acidic, thereby impairing their function, whereas homocysteine tended to increase lysosome content. Levodopa is a critically important drug for the treatment of PD. However, our data suggest that at concentrations observed in the patient, it has deleterious effects on sensory neurons that are not related to homocysteine. Full article
(This article belongs to the Special Issue Lysosomes and Diseases Associated with Its Dysfunction)
Show Figures

Figure 1

Figure 1
<p>Primary cultures of DRGs were prepared and treated for 24 h or 7 days in hypoxia (hypoxia to mimic endogenous conditions and prevent levodopa auto-oxidation). Cultures were then examined for mitochondrial membrane potential (tetramethylrhodamine, methyl ester (TMRM)), reactive oxygen species (ROS) using dihydroethidium, beta III tubulin and lysosome content using Lysotracker red (red dots in the green DRG soma) and lysosome acidity (Lysotracker red + Lysosensor green, red + green = yellow dots in green DRG soma) as detailed in the text. Cells from the 50B11 cell line were also treated, then cultured in hypoxia for 24 h, and lysosome content was examined, as detailed in the text, using Lysotracker (red dots in the cell soma at top right). Figure made using BioRender.</p>
Full article ">Figure 2
<p>Time-dependent cytotoxicity of rotenone in DRGs. Cells were fixed and stained for MAP2, a pan-neuronal marker. (<b>A</b>–<b>F</b>) Example photomicrographs following 7 days (168 h) of treatment; (<b>A</b>) = control, (<b>B</b>) = 1 nM, (<b>C</b>) = 10 nM, (<b>D</b>) = 100 nM, (<b>E</b>) = 500 nM, (<b>F</b>) = 1 µM. Scale bar in (<b>F</b>) = 200 µm and is for all photomicrographs. Photomicrographs are not edited except for contrast, and they depict the MAP2 channel. The graph shows the time-dependent effect of rotenone on DRGs. Symbols in white and shades of grey to black show data from individual technical replicates. Symbols in shades of orange to brown show experimental means. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, **** <span class="html-italic">p</span> &lt; 0.0001.</p>
Full article ">Figure 3
<p>Effect of levodopa on mitochondrial membrane potential (ΔΨ<sub>M</sub>) in primary sensory neurons (DRGs) cultured in hypoxia. Data are normalized to percent of control cells treated with 0 µM levodopa and 0 nM rotenone in hypoxia. (<b>A</b>) A dose of 30 µM levodopa increases ΔΨ<sub>M</sub> at 24 h in hypoxia; however, this effect is lost at 7 days and instead 300 µM levodopa inhibits ΔΨ<sub>M</sub>. Photomicrographs show TMRM staining in DRG soma treated with 0 µM levodopa (left) or 300 µM levodopa (LD, right) in hypoxia. Scale bar = 10 µm, for both images. (<b>B</b>) (left) Beta III tubulin immunocytochemistry shows no effect of high-dose (300 µM) levodopa on soma size; however, mean percent fluorescence for ATP5b (right), a mitochondrial marker, was reduced. (<b>C</b>) No impact of levodopa is observed in the context of parkinsonism (rotenone) at 24 h. (<b>D</b>) At 7 days, the deleterious effect of 300 µM levodopa is maintained in mild ΔΨ<sub>M</sub> inhibition (1 nM rotenone). Further, both 30 µM and 300 µM levodopa reduce ΔΨ<sub>M</sub> caused by 10 nM rotenone. No additive effects of levodopa are observed at stronger ΔΨ<sub>M</sub> inhibition caused by 500 nM rotenone. Data in (<b>A</b>–<b>D</b>) are shown as box plots of technical replicates with whiskers depicting 5–95% percentiles, black circles depicting remaining data points, lines depicting medians and “+” symbols depicting means. Light and dark orange circles show experiment means. (<b>A</b>,<b>C</b>,<b>D</b>): dashed lines show 100% (mean of control cells not treated with levodopa or rotenone) for reference. * <span class="html-italic">p</span> &lt; 0.05, *** <span class="html-italic">p</span> &lt; 0.001, **** <span class="html-italic">p</span> &lt; 0.0001.</p>
Full article ">Figure 4
<p>Effect of levodopa on oxidative stress in primary sensory neurons (DRGs) cultured in hypoxia. (<b>A</b>) Alone, only the highest concentration of levodopa (300 µM) induces mild oxidative stress. (<b>B</b>) In the context of parkinsonism (rotenone), levodopa increases oxidative stress at 1 nM rotenone. At moderate mitochondrial inhibition (10 nM, 100 nM), levodopa tended to reduce oxidative stress, possibly due to its ability to accept electrons [<a href="#B33-biology-13-00893" class="html-bibr">33</a>] and this effect is lost at 500 nM rotenone. Data are technical replicates and are shown as box plots with whiskers depicting 5–95% percentiles, black circles depicting remaining data points, lines depicting medians and “+” symbols depicting means. Light and dark orange circles show means for each experiment. *** <span class="html-italic">p</span> &lt; 0.001, **** <span class="html-italic">p</span> &lt; 0.0001 post hoc tests, following ANOVA, as discussed in text. Photomicrograph for 0 µM levodopa shows example original image of cells treated with 0 µM levodopa for 7 days and stained using dihydroethidium, with outlined area shown zoomed in and its corresponding segmentation; no cells were positive for oxidative stress. Photomicrograph for 300 µM levodopa shows example original image of cells treated with 300 µM levodopa for 7 days, then stained with dihydroethidium, with outlined area shown zoomed in and its corresponding segmentation; two cells were positive for oxidative stress in the zoomed in area. Arrowheads in photomicrographs point to DRG soma negative for oxidative stress (e.g., 0 µM levodopa). Arrows in photomicrographs point to DRG soma positive for oxidative stress. Photomicrographs are not modified, except for cropping for the zoomed images. Image processing picked out only DRG soma that contained reactive oxygen species. Note that the segmentation was for the entire image; here, we have used zoomed in areas to better demonstrate the segmentation. Scale bars = 200 µm.</p>
Full article ">Figure 5
<p>Effect of levodopa on beta III tubulin in primary sensory neurons (DRGs) cultured in hypoxia. (<b>A</b>) Alone, 3µM and 30 µM levodopa increased percent area immunoreactive for beta III tubulin. (<b>B</b>) In the context of parkinsonian sensory neurons (treated with rotenone), levodopa tended to increase percent area positive for beta III tubulin at 30 µM and 300 µM. (<b>C</b>) We examined fluorescence intensity for beta III tubulin, at the level of individual neurites in cells. Cells treated with levodopa only again showed increased fluorescence at 30 µM. (<b>D</b>) In the context of parkinsonian sensory neurons (treated with rotenone), 30 µM and 300 µM levodopa tended to increase fluorescence for beta III tubulin. Data are technical replicates shown as box plots with whiskers depicting 5–95% percentiles, black circles depicting remaining data points, lines depicting medians and “+” symbols depicting means. Light orange circles depict experimental means. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 post hoc tests, following ANOVA, as discussed in text. Photomicrographs show example original images of cells treated for 24 h in hypoxia with 0 µM, 3 µM, 30 µM, 300 µM levodopa, only, then stained for beta III tubulin. Photomicrographs are not modified. Scale bar bottom right = 200 µm, for all images.</p>
Full article ">Figure 6
<p>Effect of levodopa alone on lysosome content and acidity in primary DRGs cultured in hypoxia for 7 days. (<b>A</b>) A dose of 300 µM levodopa reduced lysosome content in DRG soma. (<b>B</b>) Acidity of lysosomes was impaired by 300 µM levodopa, because less lysosomes labelled with Lysotracker were co-labelled with Lysosensor. Data are shown as box plots with whiskers depicting 5–95% percentiles, black circles depicting remaining data points, lines depicting medians and “+” symbols depicting means. *** <span class="html-italic">p</span> &lt; 0.001. Orange circles show experiment means. Photomicrographs depict control (left) and levodopa-treated (right) soma. Lysosomes were identified as Lysotracker (red)-positive puncta, and Lysosensor (green) was used to show appropriate acidity; thus, properly acidified lysosomes show co-localised (yellow) puncta. Scale bar = 10 µm, for both images.</p>
Full article ">Figure 7
<p>Effect of levodopa on lysosomes in the 50B11 immortalised sensory cell line, treated and incubated in hypoxia for 24 h. (<b>A</b>) A dose of 300 µM levodopa reduced lysosome content in comparison to control-treated cells and cells treated with 30 µM levodopa. (<b>B</b>) Both 30 µM and 300 µM levodopa reduced lysosome content when cells are treated with entacapone. (<b>C</b>) Photomicrographs show example images of cells treated with 0 µM or 300 µM levodopa for 24 h in hypoxia and labelled with Lysotracker (red) and Hoechst (nuclei). Photomicrographs are not modified except for brightness and contrast. Scale bar = 20 µm, for both photomicrographs. Outlines show examples of CellProfiler segmentations of lysosomes (red) at 20 pixels and 60 pixels from individual nuclei (blue). Note: For segmentation, the entire nucleus was required to be within the field of view, and not to touch the image border. The green lines show the appropriate boundaries. (<b>D</b>) Individual lysosome size per boundary, showing that in the context of entacapone, 300 µM levodopa in particular reduces lysosome size. (<b>E</b>) Number of lysosomes per boundary. In the context of entacapone, both 30 µM and 300 µM levodopa reduce lysosome number. Data in graphs are shown as box plots with whiskers depicting 5–95% percentiles, black circles depicting remaining data points, lines depicting medians and “+” symbols depicting means. * <span class="html-italic">p</span> &lt; 0.05, **<span class="html-italic">p</span> &lt; 0.01, ***<span class="html-italic">p</span> &lt; 0.001, ****<span class="html-italic">p</span> &lt; 0.0001. Light orange circles show experiment means. Entacapone = 1 µM [<a href="#B38-biology-13-00893" class="html-bibr">38</a>].</p>
Full article ">
16 pages, 12495 KiB  
Article
Design and Analysis of a Hand-Held Surgical Forceps with a Force-Holding Function
by Yang Bai, Yang Yu and Zhenbang Xu
Sensors 2024, 24(18), 5895; https://doi.org/10.3390/s24185895 - 11 Sep 2024
Viewed by 836
Abstract
Physiological hand tremors, twitching, and the nonlinear characteristics of the relationship between surgical forceps clamping force and operating force seriously affect the clamping accuracy of surgical instruments. To address this problem, a new type of surgical forceps with a force-holding function was developed [...] Read more.
Physiological hand tremors, twitching, and the nonlinear characteristics of the relationship between surgical forceps clamping force and operating force seriously affect the clamping accuracy of surgical instruments. To address this problem, a new type of surgical forceps with a force-holding function was developed to replace traditional forceps, which was studied in terms of structural design, statics, and dynamics. The overall structure of the surgical forceps was designed based on the lever principle, the kinematic model of the clamping part of the surgical forceps was established by the geometrical method, and the correctness of the kinematic model was verified by ADAMS. To address the clamping accuracy of the surgical forceps, a stress analysis was performed, its dynamics model was established, a finite element simulation was performed, the modal of the forceps was optimized using the Box–Behnken method, and, finally, an experimental platform was built to perform the accuracy test. The results demonstrate that the designed surgical forceps exhibit high clamping accuracy and fulfill the design specifications for surgical operations. Full article
(This article belongs to the Section Biomedical Sensors)
Show Figures

Figure 1

Figure 1
<p>Overall structure of the surgical forceps.</p>
Full article ">Figure 2
<p>Pseudo-rigid body model of the surgical forceps.</p>
Full article ">Figure 3
<p>Comparison of the kinematic modeling and simulation of the clamping action.</p>
Full article ">Figure 4
<p>Comparison of the kinematic modeling and simulation of release action.</p>
Full article ">Figure 5
<p>Simplified model of the arm under the forceps.</p>
Full article ">Figure 6
<p>Force clouds for two limit states of the forceps.</p>
Full article ">Figure 7
<p>Three-dimensional response surface of the fundamental frequency.</p>
Full article ">Figure 8
<p>Optimal values of hinge parameters.</p>
Full article ">Figure 9
<p>Fundamental frequency in two limit states of the forceps.</p>
Full article ">Figure 10
<p>Fundamental frequency of the forceps.</p>
Full article ">Figure 11
<p>Experimental test platform.</p>
Full article ">Figure 12
<p>Variation in the gripping force of the forceps.</p>
Full article ">Figure 13
<p>Variation of clamping force with time for long clamping times.</p>
Full article ">
14 pages, 2097 KiB  
Article
Do Hand Exercises Influence Physiological Hand Tremor? An Observational Cohort Study on Healthy Young Adults
by Olga Papale, Francesca Di Rocco, Emanuel Festino, Viviana Gammino, Cristina Cortis and Andrea Fusco
Appl. Sci. 2024, 14(11), 4467; https://doi.org/10.3390/app14114467 - 23 May 2024
Viewed by 1758
Abstract
Physiological hand tremors appear to be one of the most common types of tremors that occur during the lifespan. Activities most prominently affected by hand tremors are those involving the movement of small muscles, such as fine motor skills, which in turn could [...] Read more.
Physiological hand tremors appear to be one of the most common types of tremors that occur during the lifespan. Activities most prominently affected by hand tremors are those involving the movement of small muscles, such as fine motor skills, which in turn could be influenced by several factors, including lateral dominance. The difference in skills due to lateral dominance is defined as inter-limb imbalance or inter-limb asymmetry. When this asymmetry is attributed to the tremor and the difference in tremor between the limbs, it could be defined as the inter-limb asymmetry of tremors. This study aimed to evaluate the acute effects of wobble-board hand exercise training on the inter-limb asymmetry of tremors. Thirty-two (eighteen males and fourteen females) participants (age: 25.2 ± 2.6 years, weight: 63.9 ± 10.5 kg, height: 1.66 ± 0.8 m, and BMI: 22.8 ± 2.3 kg/m2) were involved in the study. Before (PRE) and after (POST) the wobble-board hand exercises, postural hand tremor was evaluated using a tri-axial accelerometer fixed under the palm. Recordings were taken for 15 s. One-way Analysis of Variance (ANOVA) was used to examine the effects of hand exercises on inter-limb (dominant vs. non-dominant) asymmetry of tremor in testing time (PRE vs. POST) in relation to sex (male vs. female). The statistical significance was set at p < 0.05. Significant differences were found in physiological hand tremors between limbs (dominant vs. non-dominant) in the PRE evaluation (p = 0.03) independently from sex while no differences were found in the POST evaluation. A significant difference emerged in the PRE evaluation for males (p = 0.04) and females (p = 0.03) in relation to the testing time and preferred hand. This difference was no longer present in the POST evaluation. In conclusion, wobble-board hand exercises could represent an effective strategy to reduce inter-limb asymmetry. These results emphasize the importance of task-specific training to maximize the reduction in inter-limb asymmetry of tremors following wobble-board hand exercises. Full article
(This article belongs to the Special Issue Applied Biomechanics and Motion Analysis)
Show Figures

Figure 1

Figure 1
<p>Timeline of the experimental procedures.</p>
Full article ">Figure 2
<p>Tri-axial accelerometer attached to the hand using the customized elastic belt (<b>a</b>). Starting (<b>b</b>) and recording (<b>c</b>) positions of the hand during physiological hand tremor measurement.</p>
Full article ">Figure 3
<p>Standard upper-limb wobble-board hand exercise position with the working limb placed at 90° on the wobble board and the contralateral one resting on the same side (<b>a</b>) with the monitor at eye level 2 m away (<b>b</b>).</p>
Full article ">Figure 4
<p>Means and standard deviations of the acceleration during tremor before (PRE) and after (POST) the wobble-board hand exercise for dominant and non-dominant limbs. * Significant differences between dominant and non-dominant limbs.</p>
Full article ">Figure 5
<p>Means and standard deviations of the acceleration during tremor before (PRE) and after (POST) the wobble-board hand exercises in male and female participants. * Significant differences between male and female participants.</p>
Full article ">Figure 6
<p>Means and standard deviations of the acceleration during tremor before (PRE) and after (POST) the wobble-board hand exercises in male and female participants for dominant and non-dominant limbs. * Significant differences between dominant and non-dominant limbs for males and females, respectively.</p>
Full article ">
17 pages, 900 KiB  
Article
Two-Stage Convolutional Neural Network for Classification of Movement Patterns in Tremor Patients
by Patricia Weede, Piotr Dariusz Smietana, Gregor Kuhlenbäumer, Günther Deuschl and Gerhard Schmidt
Information 2024, 15(4), 231; https://doi.org/10.3390/info15040231 - 18 Apr 2024
Viewed by 1276
Abstract
Accurate tremor classification is crucial for effective patient management and treatment. However, clinical diagnoses are often hindered by misdiagnoses, necessitating the development of robust technical methods. Here, we present a two-stage convolutional neural network (CNN)-based system for classifying physiological tremor, essential tremor (ET), [...] Read more.
Accurate tremor classification is crucial for effective patient management and treatment. However, clinical diagnoses are often hindered by misdiagnoses, necessitating the development of robust technical methods. Here, we present a two-stage convolutional neural network (CNN)-based system for classifying physiological tremor, essential tremor (ET), and Parkinson’s disease (PD) tremor. Employing acceleration signals from the hands of 408 patients, our system utilizes both medically motivated signal features and (nearly) raw data (by means of spectrograms) as system inputs. Our model employs a hybrid approach of data-based and feature-based methods to leverage the strengths of both while mitigating their weaknesses. By incorporating various data augmentation techniques for model training, we achieved an overall accuracy of 88.12%. This promising approach demonstrates improved accuracy in discriminating between the three tremor types, paving the way for more precise tremor diagnosis and enhanced patient care. Full article
(This article belongs to the Special Issue Signal Processing and Machine Learning, 2nd Edition)
Show Figures

Figure 1

Figure 1
<p>Overall procedures in tremor classification based on a two-stage 2D-CNN. The acceleration signals are first preprocessed to extract features and calculate spectrograms. Features and spectrograms are calculated each from the hand of the more-affected side (mas) and the less-affected side (las). These two representations serve as input to two different CNNs. The first CNN distinguishes between physiological and pathological tremor. If the result is a pathological tremor, a second CNN with the same inputs is used to differentiate between ET and PD.</p>
Full article ">Figure 2
<p>Visualization of the difference by a logarithmic frequency axis in spectrograms. (<b>a</b>) Spectrogram of an acceleration-tremor signal with linear frequency axis. (<b>b</b>) Spectrogram of an acceleration-tremor signal with logarithmic frequency axis.</p>
Full article ">Figure 3
<p>Architecture of both CNN models.</p>
Full article ">Figure 4
<p>Accuracy and loss curves of the training processes. (<b>a</b>) Accuracy of training and validation for the model classifying physiological and pathological tremor. (<b>b</b>) Loss of training and validation for the model classifying physiological and pathological tremor. (<b>c</b>) Accuracy of training and validation for the model classifying ET and PD. (<b>d</b>) Loss of training and validation for the model classifying ET and PD.</p>
Full article ">Figure 5
<p>Confusion matrix of the classification of all three classes by the two-stage model using real test data of the dataset. There was no data augmentation used for the results shown in this figure.</p>
Full article ">
10 pages, 925 KiB  
Article
The Effects of Hand Tremors on the Shooting Performance of Air Pistol Shooters with Different Skill Levels
by Yu Liu, Nijia Hu, Mengzi Sun, Feng Qu and Xinglong Zhou
Sensors 2024, 24(8), 2438; https://doi.org/10.3390/s24082438 - 11 Apr 2024
Viewed by 1384
Abstract
Physiologic hand tremors are a critical factor affecting the aim of air pistol shooters. However, the extent of the effect of hand tremors on shooting performance is unclear. In this study, we aim to explore the relationship between hand tremors and shooting performance [...] Read more.
Physiologic hand tremors are a critical factor affecting the aim of air pistol shooters. However, the extent of the effect of hand tremors on shooting performance is unclear. In this study, we aim to explore the relationship between hand tremors and shooting performance scores as well as investigate potential links between muscle activation and hand tremors. In this study, 17 male air pistol shooters from China’s national team and the Air Pistol Sports Center were divided into two groups: the elite group and the sub-elite group. Each participant completed 40 shots during the experiment, with shooters’ hand tremors recorded using three-axis digital accelerometers affixed to their right hands. Muscle activation was recorded using surface electromyography on the right anterior deltoid, posterior deltoid, biceps brachii (short head), triceps brachii (long head), flexor carpi radialis, and extensor carpi radialis. Our analysis revealed weak correlations between shooting scores and hand tremor amplitude in multiple directions (middle-lateral, ML: r2 = −0.22, p < 0.001; vertical, VT: r2 = −0.25, p < 0.001), as well as between shooting scores and hand tremor complexity (ML: r2 = −0.26, p < 0.001; VT: r2 = −0.28, p < 0.001), across all participants. Notably, weak correlations between shooting scores and hand tremor amplitude (ML: r2 = −0.27, p < 0.001; VT: r2 = −0.33, p < 0.001) and complexity (ML: r2 = −0.31, p < 0.001) were observed in the elite group but not in the sub-elite group. Moderate correlation were found between the biceps brachii (short head) RMS and hand tremor amplitude in the VT and ML directions (ML: r2 = 0.49, p = 0.010; VT: r2 = 0.44, p = 0.025) in all shooters, with a moderate correlation in the ML direction in elite shooters (ML: r2 = 0.49, p = 0.034). Our results suggest that hand tremors in air pistol shooters are associated with the skill of the shooters, and muscle activation of the biceps brachii (long head) might be a factor affecting hand tremors. By balancing the agonist and antagonist muscles of the shoulder joint, shooters might potentially reduce hand tremors and improve their shooting scores. Full article
(This article belongs to the Special Issue Sensors and Wearable Technologies in Sport Biomechanics)
Show Figures

Figure 1

Figure 1
<p>The multiscale entropy curve generated from the magnitude time series.</p>
Full article ">Figure 2
<p>Scores of elite group and sub-elite group (<b>a</b>). The amplitude of hand tremors between the elite group and the sub-elite group (<b>b</b>). The peak powers of hand tremors between the elite group and the sub-elite group (<b>c</b>). The complexity of hand tremors between the elite group and the sub-elite group (<b>d</b>). * Significant tremor amplitude difference between elite group and sub-elite group: <span class="html-italic">p</span> &lt; 0.05.</p>
Full article ">Figure 3
<p>Normalized RMS of sEMG (% maximal EMG) in upper limb muscles between the elite group and the sub-elite group. * Significant tremor amplitude difference between elite group and sub-elite group: <span class="html-italic">p</span> &lt; 0.05.</p>
Full article ">
20 pages, 1741 KiB  
Article
A Machine-Learning-Based Method to Detect Degradation of Motor Control Stability with Implications to Diagnosis of Presymptomatic Parkinson’s Disease: A Simulation Study
by Vrutangkumar V. Shah, Shail Jadav, Sachin Goyal and Harish J. Palanthandalam-Madapusi
Appl. Sci. 2023, 13(17), 9502; https://doi.org/10.3390/app13179502 - 22 Aug 2023
Cited by 2 | Viewed by 1402
Abstract
Background and aim: Parkinson’s disease (PD), a neuro-degenerative disorder, is often detected by the onset of its motor symptoms such as rest tremor. Unfortunately, motor symptoms appear only when approximately 40–60% of the dopaminergic neurons in the substantia nigra are lost. In most [...] Read more.
Background and aim: Parkinson’s disease (PD), a neuro-degenerative disorder, is often detected by the onset of its motor symptoms such as rest tremor. Unfortunately, motor symptoms appear only when approximately 40–60% of the dopaminergic neurons in the substantia nigra are lost. In most cases, by the time PD is clinically diagnosed, the disease may already have started 4 to 6 years beforehand. There is therefore a need for developing a test for detecting PD before the onset of motor symptoms. This phase of PD is referred to as Presymptomatic PD (PPD). The motor symptoms of Parkinson’s Disease are manifestations of instability in the sensorimotor system that develops gradually due to the neurodegenerative process. In this paper, based on the above insight, we propose a new method that can potentially be used to detect the degradation of motor control stability, which can be employed for the detection of PPD. Methods: The proposed method tracks the tendency of a feedback control system to transition to an unstable state and uses a machine learning algorithm for its robust detection. This method is explored using a simple simulation example consisting of a simple pendulum with a proportional-integral-derivative (PID) controller as a conceptual representation for both healthy and PPD individuals with a noise variance of 0.01 and a noise variance of 0.1. The present study adopts a longitudinal design to evaluate the effectiveness of the proposed methodology. Specifically, the performance of the proposed approach, with specific choices of features, is compared to that of the Support Vector Machine (SVM) algorithm for machine learning under conditions of incremental delay-induced instability. This comparison is made with results obtained using the Longitudinal Support Vector Machine (LSVM) algorithm for machine learning, which is better suited for longitudinal studies. Results: The results of SVM with one choice of features are comparable with the results of LSVM for a noise variance of 0.01. These results are almost unaffected by a noise variance of 0.1. All of the methods showed a high sensitivity above 96% and specificity above 98% on a training data set. In addition, they perform very well with the validation synthetic data set with sensitivity above 95% and specificity above 98%. These results are robust to further increases in noise variance representing the large variances expected in patient populations. Conclusions: The proposed method is evaluated on a synthetic data set, and the machine learning results show a promise and potential for use for detecting PPD through an early diagnostic device. In addition, an example task with physiological measurement that can potentially be used as a clinical movement control test along with representative data from both healthy individuals and PD patients is also presented, demonstrating the feasibility of performing a longitudinal study to validate and test the robustness of the proposed method. Full article
(This article belongs to the Section Biomedical Engineering)
Show Figures

Figure 1

Figure 1
<p>The closed-loop feedback system representing the human sensorimotor system.</p>
Full article ">Figure 2
<p>Output of the simulation example representing data from a single clinical movement control test with different variances of noise. Here, the sensorimotor delay value is 0.105 s with the addition of system and measurement noise of variance 0, 0.01, and 0.1, respectively.</p>
Full article ">Figure 3
<p>The real part of estimated poles from the synthetic data set representing the sensorimotor loop system for ten individuals over nine time units (each unit may represent several months) for (<b>a</b>) a gradual increment in delay, and (<b>b</b>) a gradual increment in gain. Out of 10 individual data, 5 represent simulated healthy individuals (solid blue), and 5 represent simulated PPD (dashed red). These data also show the regular or irregular nature of clinical movement control tests over time units. Simulations with gradual increments in gain are at regular intervals, and simulations with gradual increments in delay are with regular and irregular intervals of clinical movement control tests. It is clear that due to the stochasticity, the trends are not clearly distinguishable (especially if there are only a few data points), and hence, a robust classification algorithm is needed.</p>
Full article ">Figure 4
<p>Effect of noise variance on the estimation of poles using MPM: (<b>a</b>) change in poles due to change in delay (<b>b</b>) change in poles due to change in gain.</p>
Full article ">Figure 5
<p>Box plot of a synthetic data set (total 1000 individuals, 500 individuals in each group) of the real part of estimated poles for 9 time units (each unit may represent several months) for simulated healthy and simulated PPD for (<b>a</b>) a gradual increment in delay and (<b>b</b>) gradual increment in gain. It is observed that the real part of the estimated poles remains in the same range for simulated healthy individuals and increases for simulated PPD over a significant period of time.</p>
Full article ">Figure 6
<p>(<b>a</b>) The pupilometer device developed in the lab that is used to collect experimental data of pupil constriction/dilation dynamics that can potentially be used as a clinical test along with the proposed method, (<b>b</b>) screenshot of the recorded video after image processing to identify and estimate the pupil diameter.</p>
Full article ">Figure 7
<p>Plots of normalized pupil diameter as a function of time for both age-matched healthy subjects (green) and PD patients (red). The plots show one subtrail each for 12 subjects with pupil diameter increasing when LED in the pupilometer device is switched off. The data are plotted after a moving-average filter is applied to smooth out the noise. The MPM method is applied to these data to estimate the poles. The machine-learning-based detection algorithm, however, cannot be applied at the moment, as that algorithm is meant to detect long-term trends with a longitudinal data set.</p>
Full article ">Figure 8
<p>Flowchart of a proposed methodology for detecting PPD in a clinical setting.</p>
Full article ">
18 pages, 3608 KiB  
Article
An Incremental Broad-Learning-System-Based Approach for Tremor Attenuation for Robot Tele-Operation
by Guanyu Lai, Weizhen Liu, Weijun Yang, Huihui Zhong, Yutao He and Yun Zhang
Entropy 2023, 25(7), 999; https://doi.org/10.3390/e25070999 - 29 Jun 2023
Cited by 1 | Viewed by 1395
Abstract
The existence of the physiological tremor of the human hand significantly affects the application of tele-operation systems in performing high-precision tasks, such as tele-surgery, and currently, the process of effectively eliminating the physiological tremor has been an important yet challenging research topic in [...] Read more.
The existence of the physiological tremor of the human hand significantly affects the application of tele-operation systems in performing high-precision tasks, such as tele-surgery, and currently, the process of effectively eliminating the physiological tremor has been an important yet challenging research topic in the tele-operation robot field. Some scholars propose using deep learning algorithms to solve this problem, but a large number of hyperparameters lead to a slow training speed. Later, the support-vector-machine-based methods have been applied to solve the problem, thereby effectively canceling tremors. However, these methods may lose the prediction accuracy, because learning energy cannot be accurately assigned. Therefore, in this paper, we propose a broad-learning-system-based tremor filter, which integrates a series of incremental learning algorithms to achieve fast remodeling and reach the desired performance. Note that the broad-learning-system-based filter has a fast learning rate while ensuring the accuracy due to its simple and novel network structure. Unlike other algorithms, it uses incremental learning algorithms to constantly update network parameters during training, and it stops learning when the error converges to zero. By focusing on the control performance of the slave robot, a sliding mode control approach has been used to improve the performance of closed-loop systems. In simulation experiments, the results demonstrated the feasibility of our proposed method. Full article
(This article belongs to the Special Issue Nonlinear Control Systems with Recent Advances and Applications)
Show Figures

Figure 1

Figure 1
<p>Tele-Operation robot system elements.</p>
Full article ">Figure 2
<p>Control mode in teleoperation systems.</p>
Full article ">Figure 3
<p>Mathematical expression of the tremor complementation model.</p>
Full article ">Figure 4
<p>Broad learning system network model architecture.</p>
Full article ">Figure 5
<p>Sparse autoencoder structure diagram.</p>
Full article ">Figure 6
<p>Block diagram of the broad-learning-system-based tremor filter.</p>
Full article ">Figure 7
<p>Expected values and actual values when the operator was operating.</p>
Full article ">Figure 8
<p>Joint angle and motion trajectory of robot manipulator with tremors and without tremors.</p>
Full article ">Figure 9
<p>The results of canceling tremors based on different approaches. (<b>a</b>) In the case of tremors, prediction values based on different approaches. (<b>b</b>) In the case of tremors, the error between tremor values and prediction values based on different approaches.</p>
Full article ">Figure 10
<p>Tremor attenuation performance based on different approaches.</p>
Full article ">Figure 11
<p>Position and velocity control resulting from applying sliding mode controller.</p>
Full article ">
30 pages, 1374 KiB  
Review
Microglia Mediated Neuroinflammation in Parkinson’s Disease
by Sevim Isik, Bercem Yeman Kiyak, Rumeysa Akbayir, Rama Seyhali and Tahire Arpaci
Cells 2023, 12(7), 1012; https://doi.org/10.3390/cells12071012 - 25 Mar 2023
Cited by 64 | Viewed by 9789
Abstract
Parkinson’s Disease (PD) is the second most common neurodegenerative disorder seen, especially in the elderly. Tremor, shaking, movement problems, and difficulty with balance and coordination are among the hallmarks, and dopaminergic neuronal loss in substantia nigra pars compacta of the brain and aggregation [...] Read more.
Parkinson’s Disease (PD) is the second most common neurodegenerative disorder seen, especially in the elderly. Tremor, shaking, movement problems, and difficulty with balance and coordination are among the hallmarks, and dopaminergic neuronal loss in substantia nigra pars compacta of the brain and aggregation of intracellular protein α-synuclein are the pathological characterizations. Neuroinflammation has emerged as an involving mechanism at the initiation and development of PD. It is a complex network of interactions comprising immune and non-immune cells in addition to mediators of the immune response. Microglia, the resident macrophages in the CNS, take on the leading role in regulating neuroinflammation and maintaining homeostasis. Under normal physiological conditions, they exist as “homeostatic” but upon pathological stimuli, they switch to the “reactive state”. Pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes are used to classify microglial activity with each phenotype having its own markers and released mediators. When M1 microglia are persistent, they will contribute to various inflammatory diseases, including neurodegenerative diseases, such as PD. In this review, we focus on the role of microglia mediated neuroinflammation in PD and also signaling pathways, receptors, and mediators involved in the process, presenting the studies that associate microglia-mediated inflammation with PD. A better understanding of this complex network and interactions is important in seeking new therapies for PD and possibly other neurodegenerative diseases. Full article
(This article belongs to the Section Cells of the Nervous System)
Show Figures

Figure 1

Figure 1
<p>M1 and M2 microglia phenotypes. Under physiological circumstances, microglia exhibit the homeostatic microglia phenotype. Depending on the environment in which they are reactive and the factors in which they are stimulated, they can change into “pro-inflammatory (M1)” or “anti-inflammatory (M2)” phenotypes. Microglia play important roles in maintaining the health of neurons, including pruning and remodeling synapses, controlling myelination, and removing pathological proteins that are misfolded through neurogenesis and phagocytosis. Microglia are also responsible for maintaining the homeostasis of brain tissue. Additionally, depending on the type of activation, microglia secrete numerous trophic factors, cytokines, and chemokines to aid in neuronal survival. Pathogenic molecules, such as LPS and/or IFN, or protein aggregates, such as α-syn, stimulate microglia into the pro-inflammatory phenotype, which then releases inflammatory molecules, such as ROS and other pro-inflammatory cytokines, including IL-1β, iNOS, TNFα, and others. Persistent exposure of microglia to these inflammatory mediators may result in neuronal damage. Contrarily, mediators, such as TGF-β, IL-4, IL-10, and IL-13, induce the M1 to M2 transition. The M2 phenotype of microglia contribute to the processes in phagocytosis, ECM rebuilding, and neuronal survival by secreting such factors as Ym1 and FIZZ1.</p>
Full article ">Figure 2
<p>Overview of microglial M1 and M2 signaling pathways in PD. The right side of the figure represents the M1 microglial phenotype and its related signaling pathways. LPS, which is one of the main M1 microglia activators, binds to MD2-bound TLR4 on the cell surface via LBP (LPS-binding protein) and CD14, which acts as a co-receptor. The resulting complex binds to TRIF and Myd88 by interacting with the cytoplasmic domain of TLRs and individual TIR domains. Activated TLR phosphorylates the IKK complex, which consists of MAP kinases, such as IKKβ, JNK, through autophosphorylation of IRAKs, thereby inducing translocation and activation of transcription factors NF-κB and AP-1 and initiates upregulation of M1-associated gene transcription. M1 activation by IFNγ occurs by initiation of the signaling pathway by IFNγR1/2, phosphorylation of STAT1 and interferon regulatory factors, and translocation to the nucleus via JAK1/2. Aggregates of α-syn released into the extracellular space bind to TLR2 following the working mechanism of TLR2s, triggering activation of NF-kB and subsequent NF-kB-dependent upregulation of NLRP3 and production of proinflammatory cytokines. NLRP3 activation provides caspase-1-mediated release of IL-1ß and IL-8. In addition, α-syn clusters are recognized by CD11b and induce mitochondrial ROS generation by impairing mitochondrial function via the Rho/ROCK pathway. In addition, the activation of the M1 phenotype contributes to the regulation of intracellular iNOS, cell surface markers (CD86, CD16/32, and MHC II), M1-related pro-inflammatory cytokines (IL-1β, IL-6, IL-12, IL-17, IL-18, IL-23, and TNFα), and chemokines (CCL2, CXCL10). The left side of the figure represents the M2 microglial phenotype and its related signaling pathways. M2 status is mainly induced by anti-inflammatory stimuli, such as IL-4, IL-10, IL-13, TGF-β, and glucocorticoids. IL-4 binds to IL-4R causing phosphorylation of JAKs/STAT6 and translocation of STAT6 to the nucleus. Activated STAT6 specifically leads to the transcription of M2-related genes, including intracellular components, such as CD206 and cytokine signal suppressor 3 (SOCS3). IL-10 binds to IL-10R1/2, enabling STAT3 to be phosphorylated and translocated to the nucleus via the JAK/STAT signal cascade and PI3K. STAT3 translocation inhibits M1-related proinflammatory cytokines and upregulation of IL-10 and TGF-β. TGF-β increases ARG1 expression and decreases iNOS and COX2. M2 microglia activation releases anti-inflammatory molecules, such as Arg-1, IGF-1, Ym1, and FIZZ1, which contribute to matrix deposition and wound healing. With the increase of the M2 phenotype, TREM2 inhibits the PI3/AKT signaling pathway, TLRs, and MAPK and provides the transition to the M2 phenotype and the inhibition of the M1 phenotype. In addition, the TREM2/DAP12 complex stimulates ERK1/2 by regulating actin polymerization and cytoskeleton with ERK1/2 activation. This activation increases the expression of CCR7 on the cell surface and provides chemotactic migration towards CCR7 ligands. In addition, TREM2 activation stimulates microglial phagocytosis in the same way. Activation of the PI3K/Akt pathway by TREM2/DAP12 contributes to the regulation of NF-κB and inhibition of TLR signaling by blocking MAPK signaling.</p>
Full article ">
19 pages, 1486 KiB  
Article
Analysis of Adaptive Algorithms Based on Least Mean Square Applied to Hand Tremor Suppression Control
by Rafael Silfarney Alves Araújo, Jéssica Cristina Tironi, Wemerson Delcio Parreira, Renata Coelho Borges, Juan Francisco De Paz Santana and Valderi Reis Quietinho Leithardt
Appl. Sci. 2023, 13(5), 3199; https://doi.org/10.3390/app13053199 - 2 Mar 2023
Cited by 4 | Viewed by 1986
Abstract
The increase in life expectancy, according to the World Health Organization, is a fact, and with it rises the incidence of age-related neurodegenerative diseases. The most recurrent symptoms are those associated with tremors resulting from Parkinson’s disease (PD) or essential tremors (ETs). The [...] Read more.
The increase in life expectancy, according to the World Health Organization, is a fact, and with it rises the incidence of age-related neurodegenerative diseases. The most recurrent symptoms are those associated with tremors resulting from Parkinson’s disease (PD) or essential tremors (ETs). The main alternatives for the treatment of these patients are medication and surgical intervention, which sometimes have restrictions and side effects. Through computer simulations in Matlab software, this work investigates the performance of adaptive algorithms based on least mean squares (LMS) to suppress tremors in upper limbs, especially in the hands. The signals resulting from pathological hand tremors, related to PD, present components at frequencies that vary between 3 Hz and 6 Hz, with the more significant energy present in the fundamental and second harmonics, while physiological hand tremors, referred to ET, vary between 4 Hz and 12 Hz. We simulated and used these signals as reference signals in adaptive algorithms, filtered-x least mean square (Fx-LMS), filtered-x normalized least mean square (Fx-NLMS), and a hybrid Fx-LMS–NLMS purpose. Our results showed that the vibration control provided by the Fx-LMS–LMS algorithm is the most suitable for physiological tremors. For pathological tremors, we used a proposed algorithm with a filtered sinusoidal input signal, Fsinx-LMS, which presented the best results in this specific case. Full article
(This article belongs to the Section Computing and Artificial Intelligence)
Show Figures

Figure 1

Figure 1
<p>Block diagram of the basic functioning of an adaptive vibration control system.</p>
Full article ">Figure 2
<p>Weight diagram of the LMS algorithm [<a href="#B26-applsci-13-03199" class="html-bibr">26</a>].</p>
Full article ">Figure 3
<p>Block diagram of Fx-LMS algorithm.</p>
Full article ">Figure 4
<p>Parkinson’s tremor signal in the time domain.</p>
Full article ">Figure 5
<p>Parkinson’s tremor signal in the frequency domain.</p>
Full article ">Figure 6
<p>Control evaluation results produced by the Fx-LMS algorithm for 30 runs of a Monte Carlo simulation.</p>
Full article ">Figure 7
<p>Behavior of the power spectral density (PSD) of the error signal by Fx-LMS.</p>
Full article ">Figure 8
<p>Control evaluation results produced by the Fx-NLMS algorithm for 30 runs of a Monte Carlo simulation.</p>
Full article ">Figure 9
<p>Behavior of the power spectral density (PSD) of the error signal by Fx-NLMS.</p>
Full article ">Figure 10
<p>Control evaluation by the Fx-LMS–NLMS algorithm for 30 runs of a Monte Carlo simulation.</p>
Full article ">Figure 11
<p>Behavior of the power spectral density (PSD) of the error signal by Fx-LMS–NLMS.</p>
Full article ">Figure 12
<p>Comparison of the normalized MSE behavior averaged over 30 runs. Ragged curves (yellow): Monte Carlo simulation of Fx-LMS. Ragged curves (blue): Monte Carlo simulation of Fx-NLMS. Ragged curves (red): Monte Carlo simulation of Fx-LMS–NLMS.</p>
Full article ">Figure 13
<p>Control evaluation results produced by the FsinX-LMS algorithm for 30 runs of a Monte Carlo simulation.</p>
Full article ">Figure 14
<p>Normalized-MSE results produced by the FsinX-LMS algorithm for 30 runs of a Monte Carlo simulation.</p>
Full article ">Figure 15
<p>Behavior of the power spectral density (PSD) of the error signal by Fx-LMS in the pathological tremor control scenario.</p>
Full article ">
10 pages, 782 KiB  
Article
The Influence of Fatigue on the Characteristics of Physiological Tremor and Hoffmann Reflex in Young Men
by Joanna Mazur-Różycka, Jan Gajewski, Joanna Orysiak, Dariusz Sitkowski and Krzysztof Buśko
Int. J. Environ. Res. Public Health 2023, 20(4), 3436; https://doi.org/10.3390/ijerph20043436 - 15 Feb 2023
Viewed by 1397
Abstract
The aim of the study was to determine the relationship between changes in physiological tremor after exercise and changes in the traction properties of the stretch reflex indirectly assessed using the Hoffmann reflex test. The research involved 19 young men practicing canoe sprint [...] Read more.
The aim of the study was to determine the relationship between changes in physiological tremor after exercise and changes in the traction properties of the stretch reflex indirectly assessed using the Hoffmann reflex test. The research involved 19 young men practicing canoe sprint (age 16.4 ± 0.7 years, body mass 74.4 ± 6.7 kg, body height 182.1 ± 4.3 cm, training experience 4.8 ± 1.6 years). During resting tests, Hoffmann reflex measurements were performed from the soleus muscle, physiological tremor of the lower limb, and the blood lactate concentration was determined. Then, a graded test was carried out on the kayak/canoe ergometer. Immediately after the exercise and in the 10th and 25th minute following the exercise, Hoffmann’s reflex of the soleus muscle was measured. The physiological tremor was measured at 5, 15 and 30 min after exercise. Blood lactate concentrations were determined immediately after physiological tremor. Both the parameters of Hoffmann’s reflex and physiological tremor changed significantly after exercise. There were no significant interrelationships between Hoffmann reflex measurements and physiological tremor in resting and post-exercise conditions. No significant correlation was detected between changes in physiological tremor and changes in Hoffmann reflex parameters. It is to be assumed that there is no connection between a stretch reflex and a physiological tremor. Full article
(This article belongs to the Special Issue Sports and Health Training—a Multidimensional Approach)
Show Figures

Figure 1

Figure 1
<p>Mean (±SD) waveforms of the spectral density function of the physiological tremor power of lower extremities.</p>
Full article ">Figure 2
<p>The course of function t(f) for illustrating the significance of tremor power increments relative to the output measurement after a step test; D1–0 for measurement 5 min after exercise, D2–0 for measurement 15 min after exercise, D3–0 for measurement 30 min after the effort; critical t-value (2.10) is represented by dashed line.</p>
Full article ">
16 pages, 2395 KiB  
Article
A Convolutional Neural Network-Based Broad Incremental Learning Filter for Attenuating Physiological Tremors in Telerobot Systems
by Guanyu Lai, Weizhen Liu, Weijun Yang and Yun Zhang
Appl. Sci. 2023, 13(2), 890; https://doi.org/10.3390/app13020890 - 9 Jan 2023
Cited by 2 | Viewed by 2324
Abstract
While master-slave teleoperated robotic systems have extensive applications in practice, the physiological tremors can easily affect the control accuracy and even destroy the stability of the closed-loop control systems during operation. Hence, the development of some effective approaches for counteracting physiological tremors is [...] Read more.
While master-slave teleoperated robotic systems have extensive applications in practice, the physiological tremors can easily affect the control accuracy and even destroy the stability of the closed-loop control systems during operation. Hence, the development of some effective approaches for counteracting physiological tremors is of both theoretical and practical importance. In this paper, a broad learning network-based filter integrating a deep learning network and modified incremental learning algorithms is proposed to reconstruct and compensate for tremor signals. To strengthen the recognition of correlations between different moments, the lateral connectivity structure is adopted to obtain multi-scale feature maps. Each feature window is obtained from multi-scale feature maps generated by the convolutional neural network, which has an advantage that makes the feature nodes fuse the feature information of long time series and short time series by the lateral connection. The broad learning network is a unique construction, which only needs to obtain the input and the output to conveniently calculate the connection weights by the pseudo-inverse without involving backpropagation. It is known that the relation between the data X and the label Y can be represented as XW=Y, and the solution W can be obtained by the pseudo-inverse W=X+Y. In addition, to guarantee the ill-posed problem, a ridge regression algorithm is used for the pseudo-inverse calculation. The effectiveness of our raised network architecture is illustrated by comparative simulation and experiment results. Full article
(This article belongs to the Section Robotics and Automation)
Show Figures

Figure 1

Figure 1
<p>Physical structure model of Touch X. (<b>a</b>) Touch X. (<b>b</b>) Structure of Touch X.</p>
Full article ">Figure 2
<p>Control mode of system.</p>
Full article ">Figure 3
<p>Control structure of the controller.</p>
Full article ">Figure 4
<p>Block diagram of the tremor filter.</p>
Full article ">Figure 5
<p>Mathematical model of the tremor filter.</p>
Full article ">Figure 6
<p>Network structure of BLS.</p>
Full article ">Figure 7
<p>Network structure of CNN-BLS.</p>
Full article ">Figure 8
<p>Process of single convolution.</p>
Full article ">Figure 9
<p>Simulated robot manipulator, motion and pose.</p>
Full article ">Figure 10
<p>The simulated result metrics of different feature nodes. (<b>a</b>) Tremor prediction by different feature nodes in the case of tremors with small amplitude and high−low frequency. (<b>b</b>) Estimation error of different feature nodes in the case of tremors with small amplitude and high−low frequency.</p>
Full article ">Figure 11
<p>The trajectory with tremor and the effect of tremor. (<b>a</b>) The signal with small amplitude and high−low frequency tremors. (<b>b</b>) The desired operation trajectory and the actual operation trajectory with small amplitude and high−low frequency tremors.</p>
Full article ">Figure 12
<p>The simulated result metrics of different algorithms. (<b>a</b>) Tremor prediction by different algorithms in the case of tremors with small amplitude and high−low frequency. (<b>b</b>) Estimation error of different algorithms in the case of tremors with small amplitude and high−low frequency.</p>
Full article ">Figure 13
<p>The trajectory with tremor and the effect of tremor attenuation. (<b>a</b>) The signal with small amplitude and high−low frequency tremors. (<b>b</b>) Tremor attenuation performance of different algorithms in the case of tremors with small amplitude and high−low frequency.</p>
Full article ">
18 pages, 3278 KiB  
Article
Identification and Characterization of Short-Term Motor Patterns in Rest Tremor of Individuals with Parkinson’s Disease
by Amanda Rabelo, João Paulo Folador, Ariana Moura Cabral, Viviane Lima, Ana Paula Arantes, Luciane Sande, Marcus Fraga Vieira, Rodrigo Maximiano Antunes de Almeida and Adriano de Oliveira Andrade
Healthcare 2022, 10(12), 2536; https://doi.org/10.3390/healthcare10122536 - 14 Dec 2022
Cited by 4 | Viewed by 1885
Abstract
(1) Background: The dynamics of hand tremors involve nonrandom and short-term motor patterns (STMPs). This study aimed to (i) identify STMPs in Parkinson’s disease (PD) and physiological resting tremor and (ii) characterize STMPs by amplitude, persistence, and regularity. (2) Methods: This study included [...] Read more.
(1) Background: The dynamics of hand tremors involve nonrandom and short-term motor patterns (STMPs). This study aimed to (i) identify STMPs in Parkinson’s disease (PD) and physiological resting tremor and (ii) characterize STMPs by amplitude, persistence, and regularity. (2) Methods: This study included healthy (N = 12, 60.1 ± 5.9 years old) and PD (N = 14, 65 ± 11.54 years old) participants. The signals were collected using a triaxial gyroscope on the dorsal side of the hand during a resting condition. Data were preprocessed and seven features were extracted from each 1 s window with 50% overlap. The STMPs were identified using the clustering technique k-means applied to the data in the two-dimensional space given by t-Distributed Stochastic Neighbor Embedding (t-SNE). The frequency, transition probability, and duration of the STMPs for each group were assessed. All STMP features were averaged across groups. (3) Results: Three STMPs were identified in tremor signals (p < 0.05). STMP 1 was prevalent in the healthy control (HC) subjects, STMP 2 in both groups, and STMP3 in PD. Only the coefficient of variation and complexity differed significantly between groups. (4) Conclusion: These results can help professionals characterize and evaluate tremor severity and treatment efficacy. Full article
Show Figures

Figure 1

Figure 1
<p>Diagram depicting the main steps for the identification and characterization of STMPs.</p>
Full article ">Figure 2
<p>Illustration of the hand positioning during the rest tasks. The inertial sensor, IMU1, was placed on the dorsal side of the hand. X, Y, and Z are the proximal–distal, medial–lateral, and dorsal–palmar orientation axes, respectively.</p>
Full article ">Figure 3
<p>The main steps in tremor data analysis of healthy individuals (yellow) and individuals with PD (gray). The tremor activity may have distinct STMPs that emerge over time. The signal is windowed, and a feature vector is estimated for each overlapping window delimited by the arrows. Black and red colors are used to ease the visualization of the boundaries of each window. The set of features is estimated for individuals in the HC and PD groups. The high-dimensional data set is reduced to a lower-dimensional space using t-SNE, allowing the identification of clusters representing distinct STMP (represented by numbers 1, 2, and 3) templates present in the tremulous activity. Once these STMP groups have been identified, it is possible to understand their dynamics over time, i.e., the likelihood of STMP appearance, persistence, and regularity.</p>
Full article ">Figure 4
<p>Calculation of the persistence time (Equation (3)) for the STMP 2. Three STMPs (represented by colors blue, yellow, and gray) were identified and distributed along the tremor signal and plotted below according to their appearance order. For STMP 2, the number of samples <math display="inline"><semantics> <mrow> <msub> <mi>n</mi> <mn>2</mn> </msub> </mrow> </semantics></math> was 20, the number of permanence blocks was 6, and the calculated persistence time was 0.2 ms.</p>
Full article ">Figure 5
<p>Silhouette plot indicating that the optimal number of clusters (k) equals to 3.</p>
Full article ">Figure 6
<p>Distribution in three STMPs of all signal segments of both groups (HC and PD). The black circles highlight the cluster centers estimated by <span class="html-italic">k</span>−means. The STMP 1 (blue) has a predominance of individuals from control group. STMP 2 (yellow) has both experimental groups, while in STMP 3 (gray) most STMPs are from individuals with PD.</p>
Full article ">Figure 7
<p>Frequency of STMPs based on each experimental group.</p>
Full article ">Figure 8
<p>STMPs distributed along the tremor time series obtained from the gyroscope axis X. (<b>A</b>) Tremor signal from a healthy individual with the prevalence of STMP 1. (<b>B</b>) Tremor signal from a healthy individual with STMPs of all types. However, most of them are STMP 1 and 2. (<b>C</b>) Tremor signal from an individual with PD. Most of the STMPs are type 2. (<b>D</b>) Severe tremor signal from an individual with PD with the prevalence of STMPs type 3.</p>
Full article ">Figure 9
<p>Transition probability between the STMP for each group (HC and PD).</p>
Full article ">Figure 10
<p>Mean of permanence time in each STMP for both groups.</p>
Full article ">
28 pages, 3062 KiB  
Article
Propranolol Modulates Cerebellar Circuit Activity and Reduces Tremor
by Joy Zhou, Meike E. Van der Heijden, Luis E. Salazar Leon, Tao Lin, Lauren N. Miterko, Dominic J. Kizek, Ross M. Perez, Matea Pavešković, Amanda M. Brown and Roy V. Sillitoe
Cells 2022, 11(23), 3889; https://doi.org/10.3390/cells11233889 - 1 Dec 2022
Cited by 4 | Viewed by 3226
Abstract
Tremor is the most common movement disorder. Several drugs reduce tremor severity, but no cures are available. Propranolol, a β-adrenergic receptor blocker, is the leading treatment for tremor. However, the in vivo circuit mechanisms by which propranolol decreases tremor remain unclear. Here, we [...] Read more.
Tremor is the most common movement disorder. Several drugs reduce tremor severity, but no cures are available. Propranolol, a β-adrenergic receptor blocker, is the leading treatment for tremor. However, the in vivo circuit mechanisms by which propranolol decreases tremor remain unclear. Here, we test whether propranolol modulates activity in the cerebellum, a key node in the tremor network. We investigated the effects of propranolol in healthy control mice and Car8wdl/wdl mice, which exhibit pathophysiological tremor and ataxia due to cerebellar dysfunction. Propranolol reduced physiological tremor in control mice and reduced pathophysiological tremor in Car8wdl/wdl mice to control levels. Open field and footprinting assays showed that propranolol did not correct ataxia in Car8wdl/wdl mice. In vivo recordings in awake mice revealed that propranolol modulates the spiking activity of control and Car8wdl/wdl Purkinje cells. Recordings in cerebellar nuclei neurons, the targets of Purkinje cells, also revealed altered activity in propranolol-treated control and Car8wdl/wdl mice. Next, we tested whether propranolol reduces tremor through β1 and β2 adrenergic receptors. Propranolol did not change tremor amplitude or cerebellar nuclei activity in β1 and β2 null mice or Car8wdl/wdl mice lacking β1 and β2 receptor function. These data show that propranolol can modulate cerebellar circuit activity through β-adrenergic receptors and may contribute to tremor therapeutics. Full article
(This article belongs to the Special Issue Cerebellar Development in Health and Disease)
Show Figures

Figure 1

Figure 1
<p><b>Propranolol reduces pathological tremor in <span class="html-italic">Car8<sup>wdl/wdl</sup></span> mice and physiological tremor in control mice.</b> (<b>A</b>) Schematic of the tremor monitor configuration. (<b>B</b>) Representative raw traces of tremor readings recorded from the tremor monitor for control mice at baseline (pink, N = 12), control mice after propranolol treatment (green, N = 12), <span class="html-italic">Car8<sup>wdl/wdl</sup></span> mice at baseline (orange, N = 12), and <span class="html-italic">Car8<sup>wdl/wdl</sup></span> mice after propranolol treatment (blue, N = 12). Larger vertical deflections indicate stronger tremor power. Scale bar is 50 mV vertical and 500 ms horizontal. (<b>C</b>) Line graph depicting tremor power versus frequency. Color representation for groups is maintained from panel (<b>B</b>). Power indicates the presence and severity level of tremor, with higher power illustrating stronger severity. Frequency indicates the speed of tremor movements. Following propranolol treatment, both control and <span class="html-italic">Car8<sup>wdl/wdl</sup></span> mice exhibit reduced tremor power compared to baseline. (<b>D</b>) Bar graph showing quantifications of peak tremor power at baseline and after propranolol treatment in control and <span class="html-italic">Car8<sup>wdl/wdl</sup></span> mice. Circle and square points represent each individual subject’s peak tremor power for control and <span class="html-italic">Car8<sup>wdl/wdl</sup></span> mice, respectively, with lines connecting each animal’s data before and after treatment. <span class="html-italic">Car8<sup>wdl/wdl</sup></span> mice exhibit significantly stronger peak tremor power at baseline compared to control mice. Following treatment with propranolol, both groups show significantly decreased maximum tremor power. * = <span class="html-italic">p</span> &lt; 0.05; **** = <span class="html-italic">p</span> &lt; 0.0001; ns = not significant, <span class="html-italic">p</span> &gt; 0.05. (<b>E</b>) Schematic illustrating the procedure for a non-tremor movement detection analysis within tremor monitor recordings. Scale bar is 1 s. (<b>F</b>) Quantifications of non-tremor movements show no significant difference between control and <span class="html-italic">Car8<sup>wdl/wdl</sup></span> mice at baseline, or within groups following propranolol treatment, indicating that tremor severity is not associated with the overall amount of non-tremor movements as captured in the recordings.</p>
Full article ">Figure 2
<p><b>General activity levels, gross locomotor activity, and gait parameters are unaffected by propranolol.</b> (<b>A</b>) Representative traces of open field activity patterns over a 30 min recording in control mice at baseline (pink, N = 18) and with propranolol (green, N = 8), and in <span class="html-italic">Car8<sup>wdl/wdl</sup></span> mice at baseline (orange, N = 20) and with propranolol (blue, N = 8). Lines indicate the animal’s locomotor trajectory over time. The same color assignment for each group is maintained throughout the remaining figure panels (legend above open field traces). Open field data from control and <span class="html-italic">Car8<sup>wdl/wdl</sup></span> mice without propranolol (pink and orange) is newly analyzed from the dataset published in Miterko et al., 2021. (<b>B</b>) Quantifications of open field activity in control and <span class="html-italic">Car8<sup>wdl/wdl</sup></span> mice. There is no significant difference in total movement time or number of movement episodes between control and <span class="html-italic">Car8<sup>wdl/wdl</sup></span> mice at baseline or with propranolol treatment, both within and across groups. No significant difference was found in ambulatory activity with or without propranolol within groups in control or <span class="html-italic">Car8<sup>wdl/wdl</sup></span> mice, or with propranolol between groups. * = <span class="html-italic">p</span> &lt; 0.05; *** = <span class="html-italic">p</span> &lt; 0.001; ns = not significant, <span class="html-italic">p</span> &gt; 0.05. (<b>C</b>) Representative traces of forepaw footprinting assays recorded from control (N = 9) and <span class="html-italic">Car8<sup>wdl/wdl</sup></span> mice (N = 9), before and after propranolol. Hindpaw prints are shown in purple for context. The 3 gait parameters assessed are stride (the distance between steps of the same paw), sway (the distance between left and right paw placement), and stance (the hypotenuse of stride and sway). Scale bar is 1 cm. (<b>D</b>) Quantifications of footprinting assays for the forepaws. Lines connect before and after treatment data for each animal. There is no significant difference within or between groups in control and <span class="html-italic">Car8<sup>wdl/wdl</sup></span> mice, before and after propranolol, for stride or stance. However, sway distances are significantly increased in <span class="html-italic">Car8<sup>wdl/wdl</sup></span> mice compared to control mice between groups, before and after propranolol. There is no significant sway difference within groups after propranolol treatment compared to baseline levels in both control and <span class="html-italic">Car8<sup>wdl/wdl</sup></span> mice.</p>
Full article ">Figure 3
<p><b>Propranolol modulates cerebellar Purkinje cell firing activity.</b> (<b>A</b>) Top, schematic of awake in vivo electrophysiology recording setup. Bottom, illustrations of a Purkinje cell (bright pink), and downstream cerebellar nuclei neuron (purple), and the two different types of action potentials Purkinje cells produce—simple spikes and complex spikes. (<b>B</b>) Representative raw electrophysiological traces of Purkinje cell activity in control mice before (pink, N = 8, n = 14) and after propranolol treatment (green, N = 5, n = 13), and <span class="html-italic">Car8<sup>wdl/wdl</sup></span> mice before (gold, N = 6, n = 14) and after propranolol treatment (blue, N = 4, n = 12). The line graph shown at the top for each condition represents the mean firing rate in Hz at each point in time for the 5 s spike traces shown below each line graph. Below the 5 s spike traces are magnified views of the spikes within the outlined boxes, spanning 500 ms. The same color assignment for each group is maintained throughout the remaining figure panels (legend above electrophysiology graphs). (<b>C</b>) Quantifications of Purkinje cell simple spike firing activity. Propranolol significantly reduces simple spike firing rate in both control and <span class="html-italic">Car8<sup>wdl/wdl</sup></span> Purkinje cells. The mode ISI<sup>−1</sup> is significantly decreased in <span class="html-italic">Car8<sup>wdl/wdl</sup></span> simple spikes following propranolol treatment but not in controls. Simple spike CV and CV2 measures do not significantly change with propranolol in both control and <span class="html-italic">Car8<sup>wdl/wdl</sup></span> mice. * = <span class="html-italic">p</span> &lt; 0.05; ** = <span class="html-italic">p</span> &lt; 0.01; *** = <span class="html-italic">p</span> &lt; 0.001; **** = <span class="html-italic">p</span> &lt; 0.0001; ns = not significant, <span class="html-italic">p</span> &gt; 0.05. (<b>D</b>) Quantifications of Purkinje cell complex spike firing activity. Propranolol significantly reduces complex spike firing rate in both control and <span class="html-italic">Car8<sup>wdl/wdl</sup></span> Purkinje cells. The mode ISI<sup>−1</sup> is significantly decreased in both control and <span class="html-italic">Car8<sup>wdl/wdl</sup></span> complex spikes following propranolol treatment. Complex spike CV is significantly reduced in <span class="html-italic">Car8<sup>wdl/wdl</sup></span> mice only, but not in controls. Complex spike CV2 measures do not significantly change with propranolol in both control and <span class="html-italic">Car8<sup>wdl/wdl</sup></span> mice.</p>
Full article ">Figure 4
<p><b>Propranolol modulates cerebellar nuclei neuron firing activity.</b> (<b>A</b>) Top, schematic of awake in vivo electrophysiology recording setup. Illustrations of a Purkinje cell (bright pink), and downstream cerebellar nuclei neuron (purple) are shown. Bottom, schematic of a coronal mouse cerebellar section with the cerebellar nuclei outlined in purple. Recordings were conducted in the interposed nucleus (IN) as shown with the electrode placement. FN = fastigial nucleus, DN = dentate nucleus. (<b>B</b>) Representative raw electrophysiological traces of cerebellar nuclei neuron activity in a control mouse before (pink, N = 6, n = 20) and after propranolol treatment (green N = 6, n = 15), and in a <span class="html-italic">Car8<sup>wdl/wdl</sup></span> mouse before (gold, N = 6, n = 15) and after propranolol treatment (blue, N = 6, n =15). The line graph shown at the top for each condition represents the mean firing rate in Hz at each point in time for the 5 s spike traces shown below each line graph. Below the 5 s spike traces are magnified views of the spikes within the outlined boxes, spanning 500 ms. The same color assignment for each group is maintained throughout the remaining figure panels (legend above electrophysiology graphs). (<b>C</b>) Quantifications of cerebellar nuclei neuron firing activity. Propranolol significantly reduces cerebellar nuclei neuron firing rate in both control and <span class="html-italic">Car8<sup>wdl/wdl</sup></span> mice. The cerebellar nuclei neuron mode ISI<sup>−1</sup> is significantly decreased in <span class="html-italic">Car8<sup>wdl/wdl</sup></span> mice following propranolol treatment but not in controls. Cerebellar nuclei neuron CV is significantly reduced in <span class="html-italic">Car8<sup>wdl/wdl</sup></span> mice only, but not in controls. Cerebellar nuclei neuron CV2 measures do not significantly change with propranolol in both control and <span class="html-italic">Car8<sup>wdl/wdl</sup></span> mice. * = <span class="html-italic">p</span> &lt; 0.05; ** = <span class="html-italic">p</span> &lt; 0.01; **** = <span class="html-italic">p</span> &lt; 0.0001; ns = not significant, <span class="html-italic">p</span> &gt; 0.05. (<b>D</b>) Linear regression models correlating mean cerebellar nuclei neuron firing parameters (firing rate, mode ISI<sup>−1</sup>, CV, and CV2) and mean average tremor power in each group. Solid black lines indicate linear model fit and dotted black lines indicate 95% confidence intervals. Only the model fit between mode ISI<sup>−1</sup> and maximal tremor power was significant (<span class="html-italic">p</span> = 0.0002).</p>
Full article ">Figure 5
<p><b>The β<sub>1</sub> and β<sub>2</sub> adrenergic receptor antibody signal is expressed throughout the cerebellar cortex.</b> (<b>A</b>,<b>E</b>) Paraffin staining of a coronal section cut through lobule VIII of the cerebellar cortex in control mice (N = 8) showing β<sub>1</sub> (<b>A</b>) and β<sub>2</sub> (<b>E</b>) adrenergic receptor antibody staining in brown. Purkinje cell somata are positioned in the Purkinje cell layer (PCL) underneath the molecular layer (ML), and directly below the PCL lies the granular layer (GL) containing granule cells and various classes of interneurons. The β<sub>1</sub> and β<sub>2</sub> signal is expressed throughout all three layers of the cerebellar cortex. Scale bar is 50 μm. (<b>B</b>–<b>B″</b>,<b>F</b>–<b>F″</b>) Free-floating fluorescence double staining of the same coronal view of lobule VIII with β<sub>1</sub> (<b>B</b>) and β<sub>2</sub> (<b>F</b>) antibody signal in green, calbindin expression in Purkinje cells in magenta (<b>B′</b>,<b>F′</b>), and the overlay of β<sub>1</sub> or β<sub>2</sub> and calbindin (<b>B″</b>,<b>F″</b>). Co-localized β<sub>1</sub> or β<sub>2</sub> and calbindin expression appears as a brighter, whitish hue. Dotted outlines in B″ and F″ indicate the areas from which the higher magnification images in (<b>C</b>–<b>C″</b>,<b>G</b>–<b>G″</b>) were taken. Scale bar is 100 μm. (<b>C</b>–<b>C″</b>,<b>G</b>–<b>G″</b>) Higher magnification image of the dotted outlined areas from (<b>B″</b>,<b>F″</b>) showing β<sub>1</sub> (<b>C</b>) and β<sub>2</sub> (<b>G</b>) signal expression in green, calbindin expression in Purkinje cells in magenta (<b>C′</b>,<b>G′</b>), and the overlay of β<sub>1</sub> or β<sub>2</sub> and calbindin (<b>C″</b>,<b>G″</b>). Dotted outlines in (<b>C</b>,<b>G</b>) indicate the area from which the higher magnification images in (<b>D</b>–<b>D″</b>,<b>H</b>–<b>H″</b>) were taken. Scale bar is 50 μm. (<b>D</b>–<b>D″, H</b>–<b>H″</b>) Even higher magnification image of the dotted outlined areas from (<b>C</b>,<b>G</b>) showing β<sub>1</sub> (<b>D</b>) and β<sub>2</sub> (<b>H</b>) signal expression in green, calbindin expression in Purkinje cells in magenta (<b>D′</b>,<b>H′</b>), and the overlay of β1 (<b>D″</b>) or β2 (<b>H″</b>) and calbindin. At these higher magnifications, the co-localization of β<sub>1</sub> or β<sub>2</sub> and calbindin expression is more easily appreciated. Scale bar is 25 μm.</p>
Full article ">Figure 6
<p><b>Propranolol does not modulate tremor, gait, or cerebellar nuclei neuron activity in mice lacking β<sub>1</sub> and β<sub>2</sub> adrenergic receptors.</b> (<b>A</b>) Representative raw traces of tremor readings recorded from the tremor monitor for <span class="html-italic">β1-AR<sup>−/−</sup>;β2-AR<sup>−/−</sup></span> mice at baseline (vermillion, N = 11), and after propranolol treatment (sky blue, N = 13). The same color assignment for each group is maintained throughout the remaining figure panels (legend below panels (<b>C</b>,<b>D</b>)). Scale bar is 50 mV vertical and 500 ms horizontal. (<b>B</b>) Line graph depicting tremor power versus frequency. Color representation for groups is maintained from panel <b>A</b>. (<b>C</b>) Bar graph showing quantifications of peak tremor power at baseline and after propranolol treatment in <span class="html-italic">β1-AR<sup>−/−</sup>;β2-AR<sup>−/−</sup></span> mice with lines connecting each animal’s data before and after treatment. There is no significant difference in peak tremor power after <span class="html-italic">β1-AR<sup>−/−</sup>;β2-AR<sup>−/−</sup></span> mice receive propranolol. * = <span class="html-italic">p</span> &lt; 0.05; **** = <span class="html-italic">p</span> &lt; 0.0001; ns = not significant, <span class="html-italic">p</span> &gt; 0.05. (<b>D</b>) Quantifications of non-tremor movements show no significant difference between <span class="html-italic">β1-AR<sup>−/−</sup>;β2-AR<sup>−/−</sup></span> mice at baseline or after being treated with propranolol. (<b>E</b>) Representative traces of forepaw footprinting assays recorded from <span class="html-italic">β1-AR<sup>−/−</sup>;β2-AR<sup>−/−</sup></span> mice before and after propranolol (N = 9). Hindpaw prints are in shown in purple for context. Scale bar is 1 cm. (<b>F</b>) Quantifications of footprinting assays. Lines connect before and after treatment data for each animal. There is no significant difference before and after propranolol for stride, stance, or sway in <span class="html-italic">β1-AR<sup>−/−</sup>;β2-AR<sup>−/−</sup></span> mice. (<b>G</b>) Representative raw electrophysiological traces of Purkinje cell activity in <span class="html-italic">β1-AR<sup>−/−</sup>;β2-AR<sup>−/−</sup></span> mice before (N = 5, n = 17) and after propranolol treatment (N = 4, n = 14). The line graph at the top for each condition represents the mean firing rate in Hz at each point in time for the 5 s spike traces shown below each line graph. Below the 5 s spike traces are magnified views of the spikes within the outlined boxes, spanning 500 ms. (<b>H</b>) Quantifications of <span class="html-italic">β1-AR<sup>−/−</sup>;β2-AR<sup>−/−</sup></span> Purkinje cell simple spike firing activity. Propranolol significantly reduces simple spike firing rate in <span class="html-italic">β1-AR<sup>−/−</sup>;β2-AR<sup>−/−</sup></span> mice. Mode ISI<sup>−1</sup>, CV, and CV2 measures are unchanged by propranolol in <span class="html-italic">β1-AR<sup>−/−</sup>;β2-AR<sup>−/−</sup></span> mice. (<b>I</b>) Quantifications of Purkinje cell complex spike firing patterns before and after propranolol treatment in <span class="html-italic">β1-AR<sup>−/−</sup>;β2-AR<sup>−/−</sup></span> mice. Propranolol significantly reduces both the firing rate and mode ISI<sup>−1</sup> of complex spikes in <span class="html-italic">β1-AR<sup>−/−</sup>;β2-AR<sup>−/−</sup></span> mice. Inversely, complex spike CV and CV2 measures are increased following propranolol treatment in <span class="html-italic">β1-AR<sup>−/−</sup>;β2-AR<sup>−/−</sup></span> mice. (<b>J</b>) Representative raw electrophysiological traces of cerebellar nuclei neuron activity in <span class="html-italic">β1-AR<sup>−/−</sup>;β2-AR<sup>−/−</sup></span> mice before (N = 6, n = 15) and after propranolol treatment (N = 4, n = 14). (<b>K</b>) Quantifications of cerebellar nuclei neuron firing activity. Propranolol has no effect on the firing rate, mode ISI<sup>−1</sup>, CV, or CV2 measures in <span class="html-italic">β1-AR<sup>−/−</sup>;β2-AR<sup>−/−</sup></span> cerebellar nuclei neurons.</p>
Full article ">Figure 7
<p><b>β<sub>1</sub> and β<sub>2</sub> adrenergic receptor function is required for propranolol to reduce <span class="html-italic">Car8<sup>wdl/wdl</sup></span> tremor.</b> (<b>A</b>) Line graph depicting tremor power versus frequency in <span class="html-italic">β1-AR<sup>−/−</sup>;β2-AR<sup>−/−</sup>;Car8<sup>wdl/wdl</sup></span> mice before (gray, N = 4) and after (indigo, N = 4) propranolol treatment. The same color assignment for each group is maintained throughout the remaining figure panels (legend below panels (<b>B</b>,<b>C</b>)). (<b>B</b>) Quantification of peak tremor power in <span class="html-italic">β1-AR<sup>−/−</sup>;β2-AR<sup>−/−</sup>;Car8<sup>wdl/wdl</sup></span> mice, with lines connecting each subject’s before and after propranolol data points. Propranolol does not significantly reduce tremor in <span class="html-italic">β1-AR<sup>−/−</sup>;β2-AR<sup>−/−</sup>;Car8<sup>wdl/wdl</sup></span> mice. ns = not significant, <span class="html-italic">p</span> &gt; 0.05. (<b>C</b>) Quantifications of non-tremor movements show no significant difference between <span class="html-italic">β1-AR<sup>−/−</sup>;β2-AR<sup>−/−</sup>;Car8<sup>wdl/wdl</sup></span> mice at baseline or after being treated with propranolol. (<b>D</b>) Representative raw electrophysiological traces of cerebellar nuclei neuron activity in <span class="html-italic">β1-AR<sup>−/−</sup>;β2-AR<sup>−/−</sup>;Car8<sup>wdl/wdl</sup></span> mice before (N = 2, n = 6) and after propranolol treatment (N = 2, n = 5). The line graph at the top for each condition represents the mean firing rate in Hz at each point in time for the 5 s spike traces shown below each line graph. Below the 5 s spike traces are magnified views of the spikes within the outlined boxes, spanning 500 ms. (<b>E</b>) Quantifications of <span class="html-italic">β1-AR<sup>−/−</sup>;β2-AR<sup>−/−</sup>;Car8<sup>wdl/wdl</sup></span> cerebellar nuclei neuron activity before and after propranolol. Propranolol has no effect on the firing rate, mode ISI<sup>−1</sup>, CV, or CV2 in <span class="html-italic">β1-AR<sup>−/−</sup>;β2-AR<sup>−/−</sup>;Car8<sup>wdl/wdl</sup></span> nuclei neurons.</p>
Full article ">
Back to TopTop