Name: digital handwriting analysis of characters in chinese patients with mild cognitive impairment
Uploaded: 2021-03-11T14:00:00
Description: Watch this Scientific Journal Video about Digital Handwriting Analysis of Characters in Chinese Patients with Mild Cognitive Impairment at JoVE.com

We thank Professor Hans-Leo Teulings from Neuroscript LLD for the digital technology support.
This study was supported by the Wu Jieping Foundation (Grant No.: 320.6750.18456).

Our study was approved by the Academic Ethics Committee of the Biological Sciences Division of the Chinese PLA General Hospital in Beijing, China.
1. General aspects of method development
<ol>
	<li>Use a USB digitizer (e.g., Wacom Cintiq Pro 16) and a handheld stylus pen for the handwriting movements. The detailed specifications of the digitizer are as follows: external dimensions (width x depth x height) 410 x 265 x 17.5 mm, spatial resolution 3840 x 2160 dots, pixel size 0.090 x 0.090 mm, ...

<ol>
	<li>Werner, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Handwriting+process+variables+discriminating+mild+Alzheimer's+disease+and+mild+cognitive+impairment.">Handwriting process variables discriminating mild Alzheimer's disease and mild cognitive impairment.</a> Journals of Gerontology. 61 (4), 228-236 (2006).</li><li>Kawa, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Spatial+and+dynamical+handwriting+analysis+in+mild+cognitive+impairment.">Spatial and dynamical handwriting analysis in mild cognitive impairment.</a> Computers in Biology and Medicine. 82, 21-28 (2017).</li><li>De Paula, J. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impairment+of+fine+motor+dexterity+in+mild+cognitive+impairment+and+Alzheimer's+disease+dementia:+association+with+activities+of+daily+living.">Impairment of fine motor dexterity in mild cognitive impairment and Alzheimer's disease dementia: association with activities of daily living.</a> Revista Brasilra De Psiquiatria. 38 (3), 235-238 (2016).</li><li>Takehiko, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Combined+effects+of+mild+cognitive+impairment+and+slow+gait+on+risk+of+dementia.">Combined effects of mild cognitive impairment and slow gait on risk of dementia.</a> Experimental Gerontology. 110, 146-150 (2018).</li><li>Impedovo, D., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dynamic+handwriting+analysis+for+the+assessment+of+neurodegenerative+diseases:+a+pattern+recognition+perspective.">Dynamic handwriting analysis for the assessment of neurodegenerative diseases: a pattern recognition perspective.</a> IEEE Reviews in Biomedical Engineering. 12, 209-220 (2019).</li><li>Yu, N. Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Characterization+of+the+fine+motor+problems+in+patients+with+cognitive+dysfunction+-+A+computerized+handwriting+analysis.">Characterization of the fine motor problems in patients with cognitive dysfunction - A computerized handwriting analysis.</a> Human Movement Science. 65 (17), 30841-30842 (2019).</li><li>Zhou, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Characteristics+of+agraphia+in+Chinese+patients+with+Alzheimer's+disease+and+amnestic+Mild+Cognitive+Impairment.">Characteristics of agraphia in Chinese patients with Alzheimer's disease and amnestic Mild Cognitive Impairment.</a> Chinese Medical Journal. 129 (13), 1553-1557 (2016).</li><li>Rosenblum, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Handwriting+process+variables+among+elderly+people+with+mild+major+depressive+disorder:+a+preliminary+study.">Handwriting process variables among elderly people with mild major depressive disorder: a preliminary study.</a> Aging Clinical &amp; Experimental Research. 22 (2), 141-147 (2010).</li><li>Caligiuri, M. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Signature+dynamics+in+Alzheimer's+disease.">Signature dynamics in Alzheimer's disease.</a> Forensic Science International. 302, 109880 (2019).</li><li>Thomas, M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Handwriting+analysis+in+Parkinson's+disease:+current+status+and+future+directions.">Handwriting analysis in Parkinson's disease: current status and future directions.</a> Movement Disorders Clinical Practice. 4 (6), 806-818 (2017).</li><li>Leung, S. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+comparative+approach+to+the+examination+of+Chinese+handwriting-The+Chinese+character.">A comparative approach to the examination of Chinese handwriting-The Chinese character.</a> Journal of the Forensic Science Society. 25, 255-267 (1985).</li><li>Ma, H. I., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Progressive+micrographia+shown+in+horizontal,+but+not+vertical,+writing+in+Parkinson's+disease.">Progressive micrographia shown in horizontal, but not vertical, writing in Parkinson's disease.</a> Behavioural Neurology. 27 (2), 169-174 (2013).</li><li>Yan, J. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Alzheimer's+disease+and+mild+cognitive+impairment+deteriorate+fine+movement+control.">Alzheimer's disease and mild cognitive impairment deteriorate fine movement control.</a> Journal of Psychiatric Research. 42, 1203-1212 (2008).</li><li>Johnson, B. P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Understanding+macrographia+in+children+with+autism+spectrum+disorders.">Understanding macrographia in children with autism spectrum disorders.</a> Research in Developmental Disabilities. 34 (9), 2917-2926 (2013).</li><li>Afonso, O., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Writing+difficulties+in+Alzheimer's+disease+and+Mild+Cognitive+Impairment.">Writing difficulties in Alzheimer's disease and Mild Cognitive Impairment.</a> Reading and Writing. 32 (1), 217-233 (2019).</li><li>Drot&#225;r, P., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evaluation+of+handwriting+kinematics+and+pressure+for+differential+diagnosis+of+Parkinson's+disease.">Evaluation of handwriting kinematics and pressure for differential diagnosis of Parkinson's disease.</a> Artificial Intelligence in Medicine. 67, 39-46 (2016).</li><li>Garre-Olmo, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Kinematic+and+pressure+features+of+handwriting+and+drawing:+preliminary+results+between+patients+with+mild+cognitive+impairment,+Alzheimer+disease+and+healthy+controls.">Kinematic and pressure features of handwriting and drawing: preliminary results between patients with mild cognitive impairment, Alzheimer disease and healthy controls.</a> Current Medicinal Chemistry. 14, 960-968 (2017).</li><li>Cohen, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Digital+clock+drawing:+differentiating+"thinking"+versus+"doing"+in+younger+and+older+adults+with+depression.">Digital clock drawing: differentiating "thinking" versus "doing" in younger and older adults with depression.</a> Journal of the International Neuropsychological Society. 20 (9), 920-928 (2014).</li><li>Rosenblum, S., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Handwriting+as+an+objective+tool+for+Parkinson's+disease+diagnosis.">Handwriting as an objective tool for Parkinson's disease diagnosis.</a> Journal of Neurology. 260 (9), 2357-2361 (2013).</li><li>Grace, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Do+handwriting+difficulties+correlate+with+core+symptomology,+motor+proficiency+and+attentional+behaviours.">Do handwriting difficulties correlate with core symptomology, motor proficiency and attentional behaviours.</a> Journal of Autism and Developmental Disorders. 47 (4), 1-12 (2017).</li><li>Petersen, R. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mild+cognitive+impairment+as+a+diagnostic+entity.">Mild cognitive impairment as a diagnostic entity.</a> Journal of Interactive Marketing. 256 (3), 183-194 (2004).</li><li>Ishikawa, T., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Handwriting+features+of+multiple+drawing+tests+for+early+detection+of+Alzheimer's+Disease:+A+preliminary+result.">Handwriting features of multiple drawing tests for early detection of Alzheimer's Disease: A preliminary result.</a> Studies in Health Technology and Informatics. 264, 168-172 (2019).</li><li>Herold, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Thinking+while+moving+or+moving+while+thinking-concepts+of+motor-cognitive+training+for+cognitive+performance+enhancement.">Thinking while moving or moving while thinking-concepts of motor-cognitive training for cognitive performance enhancement.</a> Frontiers in Aging Neuroscience. 10, 228 (2018).</li></ol>

The critical steps in the protocol confirm the legibility of &#8220;<img alt="Equation 6" src="/files/ftp_upload/61841/61841equ06.jpg" />&#8221;. In detail, within an entire character, the #3 stroke needs to be shorter than the other horizonal strokes, and the #4 stroke needs to be shorter than the #2 stroke. More specifically, more attentional resources are needed during the writing of the #3 stroke and #4 stroke6,<sup class="xref"...

Mild cognitive impairment (MCI) is considered as a transitional but progressively degenerative cognitive phase that precedes the onset of Alzheimer&#8217;s disease (AD)1. It has been reported that the AD progression rate per year is 15% while nearly 75% of moderate and severe MCI cases might remain undiagnosed2. Recent studies have reported that patients with MCI have difficulty in some aspects of fine motor tasks3, and those patients who showed motor disorders, such as slow gait, had a high risk of dementia4.
Handwriting is a complex human activity that entails an intricate blend of cognitive, kinesthetic, and perceptual-motor components including visual and kinesthetic perception, motor planning, eye-hand coordination, visual-motor integration, dexterity, and manual skills1. Handwriting analysis has been utilized to detect cognitive and motor dysfunctions in many types of neurodegenerative diseases, such as AD and Parkinson&#8217;s disease (PD)5. In addition, some aspects of handwriting problems have been reported to be an indicator for MCI and related to disease progression6. As a majority of the population uses language, studies that investigate handwriting analysis in Chinese speakers (especially simplified Chinese characters) are still lacking.
There have been several articles that have investigated handwriting abnormalities or &#8220;agraphia&#8221; in individuals with MCI. For example, by utilizing the traditional pencil&#8211;paper methods, Zhou and colleagues tried to unveil the distinct writing abilities between patients with MCI and individuals without MCI. The differences between the groups were not obvious, with the exception of writing errors7. Kawa et al. found handwriting features in patients with MCI using a smart pen, which could dynamically analyze the stroke and pen speed during writing2. WACOM hardware and MovAlyzeR software can detect more real-time information compared with traditional pencil and paper methods and smartpen paper methods. Therefore, dynamic handwriting data, such as pen-down pressure, velocity, acceleration, and jerk, have been found to be a new focus of handwriting analysis relative to static data, such as letter size and space between words2.
However, another phenomenon that cannot be overlooked is the cross-cultural effect of handwriting. The writing systems of different nations are not always the same (e.g., English letters are written from left to right while Hebrew letters are written from right to left)8. In this issue, even reviews have confirmed the effectiveness of handwriting analysis9,10 in alphabetic languages, and the wide gap between Chinese characters and western letters has hindered the interchange capability of handwriting analysis in the methods and results11 of these studies.
There exist several major dissimilarities between western languages (e.g., English) and Chinese. First, there are many more horizonal movements of the pen tip during Chinese character writing compared with letter writing12. Second, unlike the alphabet language, which is associated with phonemes, Chinese is considered to be logographic7. As a result, most Chinese characters have their own unique stroke order, and the width and height of strokes need to be strictly limited. Otherwise, unlimited widths and heights might cause increased illegibility11 (&#8220;<img alt="Equation 1" src="/files/ftp_upload/61841/61841equ01.jpg" />&#8221; and &#8220;<img alt="Equation 2" src="/files/ftp_upload/61841/61841equ02.jpg" />&#8221; are completely different Chinese characters. Also, &#8220;<img alt="Equation 3" src="/files/ftp_upload/61841/61841equ03.jpg" />&#8221;, &#8220;<img alt="Equation 4" src="/files/ftp_upload/61841/61841equ04.jpg" />&#8221;, and &#8220;<img alt="Equation 5" src="/files/ftp_upload/61841/61841equ05.jpg" />&#8221; are different Chinese characters).
&#8220;<img alt="Equation 6" src="/files/ftp_upload/61841/61841equ06.jpg" />&#8221; (pronounced &#8220;Zheng&#8221;) is a typical, simple, and commonly used Chinese character that nearly every Chinese speaker with a two-year educational level can read and write. It has been selected as a writing task in previous Chinese handwriting analysis studies6,12. Researchers decided to use &#8220;<img alt="Equation 6" src="/files/ftp_upload/61841/61841equ06.jpg" />&#8221; as the writing task because it is &#8220;square-like&#8221; and composed of five strokes, all of which are horizonal (#1, #3, #5 stroke, from left to right) or vertical (#2, #4 stroke, from up to down) (Figure 1). According to many fine motor studies, fulfilling the #3 stroke (horizonal) and the #4 stroke (vertical) requires pure wrist and finger movements, respectively6,12,13. As a result, the stroke velocity of both strokes could be a proper manifestation14.
In addition, pen pressure during handwriting is a handwriting feature that has been shown to outperform other kinematic features in reflecting motor control5,15. However, there are no relevant studies in Chinese patients, though positive results have been confirmed by research groups from the Czech Republic, Spain, Israel, and other countries8,16,17.
The signature has been commonly used as a handwriting task in numerous studies5. In general, a signature requires little thinking or in-air time18. &#8220;In-air&#8221; is defined as when the pressure of the pen tip to the screen is 0 during the handwriting, and &#8220;in-air time&#8221; is the sum of the time &#8220;in-air&#8221; during the handwriting. Individuals who suffer from many neuropsychiatric disorders might have deficits in psychomotor control, and thus they exhibit increased in-air time of the signature. For example, Rosenblum et al. found that Israeli patients with depression and Parkinson&#8217;s disease showed longer in-air time compared with healthy controls during writing their own name in Hebrew8,19. As Chinese characters have their own shape, in this study, it was decided to use the in-air length tortuosity in segmentation between characters during writing the name as a potential indicative parameter. Tortuosity, defined by the ratio of the arc length to the Euclidean distance between end points, is a measure of curvature, and therefore indexes the smoothness of a specific writing output20.

<table>
	<tbody>
		<tr>
			<td></td>
			<td>Microsoft</td>
			<td>Surface Pro 2</td>
			<td>computer</td>
		</tr>
		<tr>
			<td></td>
			<td>MovAlyeR</td>
			<td>3.4</td>
			<td>software</td>
		</tr>
		<tr>
			<td></td>
			<td>WACOM</td>
			<td>Cintiq</td>
			<td>digitizer</td>
		</tr>
	</tbody>
</table>

digital handwriting analysis of characters in chinese patients with mild cognitive impairment

An increasing amount of evidence shows that cognitive deficits and movement dysfunctions are not separated. Patients with mild cognitive impairment (MCI) can manifest fine motor disorders of the upper extremities. Handwriting is a complex and unique human activity involving both motor and cognitive coordination. Researchers from western countries have discovered that patients with MCI have abnormal handwriting features. However, no relevant studies have been conducted in the Chinese population. Owing to the cross-culture phenomenon of handwriting, the aim of this study is to find new handwriting tasks to demonstrate the differences in handwriting features between elderly patients with MCI and age-matched healthy individuals.

The demographic data of the subjects demonstrated that all the groups matched well in age, gender, educational level, dominant hand, and other parameters.
As shown in Table 1, during the writing of the Chinese character &#8220;<img alt="Equation 6" src="/files/ftp_upload/61841/61841equ06.jpg" />&#8221;, elderly subjects with MCI exhibited a lower average absolute velocity of the #3 (2.46 &#177; 0.40 vs 1.82 &#177; 0.55, P = 0.001) and #4 stroke (2.61 &#17...

Watch this Scientific Journal Video about Digital Handwriting Analysis of Characters in Chinese Patients with Mild Cognitive Impairment at JoVE.com

Digital Handwriting Analysis of Characters in Chinese Patients with Mild Cognitive Impairment

This study proposed a digital handwriting analysis of characters in individuals with mild cognitive impairment to find more information than is revealed by traditional pencil&#8211;paper handwriting analysis.

An increasing amount of evidence shows that cognitive deficits and movement dysfunctions are not separated. Patients with mild cognitive impairment (MCI) ...

Handwriting analysis has been used to detect, cognitive and motor dysfunctions. Some aspect of handwriting difficulties can be an indicator for MCI, I'm delighted to(inaudible)The main advantage of this study is that it uses a digital handwriting analysis system for simplified Chinese character users. This method can also be applied to the detection of psychomotor retardation in patients with depression, Schizophrenia, or other psychiatric disorders who are simplified Chinese users.Before beginning and analysis, select a 410 by 265 by 17.5 millimeter USB digitizer with a 3, 840 by 2, 160 dot spatial resolution, a 0.9 by 0.9 millimeter pixel size, a 30 millisecond temporal resolution, and an 8, 192 pressure level, and a handheld stylist pen for the handwriting movements. connect a laptop PC to the digitizer to collect and exhibit the handwriting traces. And install an appropriate data recording, processing, and analyzing software program.Recruit mild cognitive impairment participants who present with a memory complaint, an objectively impaired memory function, intact activity of daily living, and the absence of Dementia. To perform a handwriting task, use the stylus to create sample Chinese characters in the writing area of the digitizer. Give the digitizer and stylus to the participant and instruct the participant to use the stylus to write their name in Chinese with the dominant hand, while holding the digitizer in a comfortable position.Next, instruct the participant to use the dominant hand to write the printed version of the Chinese character, Xiang"If the character is being written in the wrong stroke order, stop the trial and trace and show the subject how to write the character in the correct stroke order. If any hesitation is derived from a lack of knowledge, stop the trial and show the participant how to write the character correctly. Then instruct the participant to use the dominant hand to sign their name in Chinese three times.To analyze the handwriting task data, in the software analysis program, right click on experiment"to select properties, processing, and segmentation. In segmentation flags"click Add first segmentation at any rate"Add last segmentation at any rate"and Move segmentation point to nearest pen down if on a pen lift"In segmentation methods"click on At pen down trajectories"and reset the previously selected segmentation flags parameters. For parameter calculation in Xiang"select the participant and click Handwriting Trials"Use the tracing system to trace the handwriting process and stroke order of Xiang"step-by-step, and locate the segmentation of stroke number three of Xiang"The average absolute velocity will be automatically calculated within the extracted data.Locate the segmentation of stroke number four of Zhang"The software will automatically calculate the average absolute velocity for strong number four. The pen pressure of each segmentation and average pen pressure will also be calculated by the software. Next, select the participant in Xiang, click handwriting trials and use the tracing system to trace the handwriting process and stroke order of the participant signature step-by-step.Locate the segmentation of the stroke between the characters. The absolute size and road length will be calculated. Then use the formula to calculate the in-air length tortuosity in the segmentation between characters, As shown in the table, during the writing of the Chinese characters Xiang, elderly subjects with mild cognitive impairment exhibited a lower average absolute velocity of the number three, a number four strokes and a higher average pen pressure compared to healthy elderly subjects.Additionally, during the signing of Chinese names, the elderly subjects with mild cognitive impairment exhibited a higher in-air length tortuosity in segmentation between the characters compared to healthy elderly subjects. The most important step is confirming the character legibility, using Xiang as example. The third stroke should be shorter than other horizontal strokes.Foreign 00:05:35

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Medicine

A Multimodal Imaging- and Stimulation-based Method of Evaluating Connectivity-related Brain Excitability in Patients with Epilepsy

Resting-state functional connectivity MRI (rs-fcMRI) is a technique that identifies connectivity between different brain regions based on correlations over time in the blood-oxygenation level dependent signal. rs-fcMRI has been applied extensively to identify abnormalities in brain connectivity in different neurologic and psychiatric diseases. However, the relationship among rs-fcMRI connectivity abnormalities, brain electrophysiology and disease state is unknown, in part because the causal significance of alterations in functional connectivity in disease pathophysiology has not been established. Transcranial Magnetic Stimulation (TMS) is a technique that uses electromagnetic induction to noninvasively produce focal changes in cortical activity. When combined with electroencephalography (EEG), TMS can be used to assess the brain's response to external perturbations. Here we provide a protocol for combining rs-fcMRI, TMS and EEG to assess the physiologic significance of alterations in functional connectivity in patients with neuropsychiatric disease. We provide representative results from a previously published study in which rs-fcMRI was used to identify regions with abnormal connectivity in patients with epilepsy due to a malformation of cortical development, periventricular nodular heterotopia (PNH). Stimulation in patients with epilepsy resulted in abnormal TMS-evoked EEG activity relative to stimulation of the same sites in matched healthy control patients, with an abnormal increase in the late component of the TMS-evoked potential, consistent with cortical hyperexcitability. This abnormality was specific to regions with abnormal resting-state functional connectivity. Electrical source analysis in a subject with previously recorded seizures demonstrated that the origin of the abnormal TMS-evoked activity co-localized with the seizure-onset zone, suggesting the presence of an epileptogenic circuit. These results demonstrate how rs-fcMRI, TMS and EEG can be utilized together to identify and understand the physiological significance of abnormal brain connectivity in human diseases.

Resting-state functional-connectivity MRI has identified abnormalities in patients with a wide range of neuropsychiatric disorders, including epilepsy due to malformations of cortical development. Transcranial Magnetic Stimulation in combination with EEG can demonstrate that patients with epilepsy have cortical hyperexcitability in regions with abnormal connectivity.

Resting-state functional connectivity MRI (rs-fcMRI) is a technique that identifies connectivity between different brain regions based on correlations ...

Application of Granger Causality Analysis of the Directed Functional Connection in Alzheimer's Disease and Mild Cognitive Impairment

Impaired functional connectivity in the Default Mode Network (DMN) may be involved in the progression of Alzheimer&#39;s Disease (AD). The Posterior Cingulate Cortex (PCC) is a potential imaging marker for monitoring the progression of AD. Previous studies did not focus on the functional connectivity between the PCC and nodes in regions outside the DMN, but our study is an effort to explore these overlooked functional connections. For collecting data, we used functional Magnetic Resonance Imaging (fMRI) and Granger Causality Analysis (GCA). fMRI provides a non-invasive method for studying the dynamic interactions between the different brain regions. GCA is a statistical hypothesis test for determining whether one-time series is useful in forecasting another. In simple terms, it is judged by comparing the &#34;Known all the information on the last moment, the distribution of the probability of X at this time&#34; and the &#34;Known all the information on the last moment except Y, the distribution of the probability of X at this time&#34;, to determine whether there is a causal relationship between Y and X. This definition is based on the complete information source and stationary chronological sequence. The main step of this analysis is to use X and Y to establish the regression equation and draw a causal relationship by a hypothetical test. Since GCA can measure causal effects, we used it to investigate the anisotropy of the functional connectivity and explore the hub function of the PCC. Here, we screened 116 participants for MRI scanning, and after preprocessing the data obtained from neuroimaging, we used GCA to derive the causal relationship of each node. Finally, we concluded that the directed connection is significantly different between the Mild Cognitive Impairment (MCI) and AD groups, both from the PCC to the whole brain and from the whole brain to the PCC.

Application of Granger Causality Analysis of the Directed Functional Connection in Alzheimer&#039;s Disease and Mild Cognitive Impairment

Based on resting-state functional magnetic resonance imaging with Granger causality analysis, we investigated the alterations in the directed functional connectivity between the posterior cingulate cortex and whole brain in patients with Alzheimer&#39;s Disease (AD), patients with Mild Cognitive Impairment (MCI), and healthy controls.

Impaired functional connectivity in the Default Mode Network (DMN) may be involved in the progression of Alzheimer&#39;s Disease (AD). The Posterior ...

Enema of Traditional Chinese Medicine for Patients with Severe Acute Pancreatitis

Severe acute pancreatitis (SAP) is characterized by high mortality rates, numerous complications, and extreme difficulties in treatment. A traditional Chinese medicine (TCM) enema has been widely utilized in clinical and experimental studies of SAP. It has been demonstrated to have beneficial effects in protecting pancreatic function and delaying disease progression. The procedure of TCM enema is to perfuse the Chinese medicinal liquid of raw rhubarb (Rheum officinale Baill. DaHuang) from the anus into the rectum and colon. Basic steps of the procedure include boiling the herbal solution in advance, using a disposable enema kit to assist patients in taking a left lying position, raising the patient's hip 10 cm, and carefully inserting the enema 30-35 cm into the anus, with a drip speed of 60-80 drops/min. The medicine liquid temperature should be equivalent to the patient's body temperature, typically between 37-39 &#176;C. The end of the enema operation should be slow, and Tui na (massage therapy) should be administered before extubation. The medication liquid should be kept in the rectum for more than 1 h. After issuing an enema, it is essential to observe the patient's feces and abdomen, and to evaluate the remission of abdominal signs and symptoms.

An enema is a type of traditional Chinese medicine (TCM) therapy used to treat severe acute pancreatitis (SAP). The therapy involves instilling a TCM liquid into the rectum and colon through the anus to keep the liquid in the intestine, absorbing through the intestinal mucosa. This study aims to standardize the enema procedure for SAP patients.

Severe acute pancreatitis (SAP) is characterized by high mortality rates, numerous complications, and extreme difficulties in treatment. A traditional ...

Tai Chi with Mindfulness Training to Manage Diabetic Peripheral Neuropathy

Effects of Mindfulness Training Combined with Tai Chi in Patients with Diabetic Peripheral Neuropathy

Diabetic peripheral neuropathy (DPN) is one of the most prevalent chronic complications of diabetes. One of its crucial therapy approaches is mind-body exercise. Recently, various exercise modalities, including stepping, resistance, aerobics, balance, and whole-body vibration, were investigated to construct the most suitable form of exercise for patients with DPN. The purpose of this study is to describe a standard protocol for mindfulness training combined with Tai Chi. The convenience sampling method was used to select 90 patients with DPN who met the inclusion and exclusion criteria from three communities. The three communities were randomly divided into the control group (CG), the Tai Chi group (TCG), and the mindfulness training combined with the Tai Chi group (MTCG). The CG was given routine health education guidance once a month, a total of three times. Based on the CG, the TCG practiced Tai Chi three times; the MTCG received mindfulness training combined with Tai Chi exercise a week for a total of 12 weeks. Before the intervention and 12 weeks after the intervention, the clinical symptoms, neurological function, attention awareness level, pain, and quality of life of the subjects were evaluated by Toronto Clinical Scoring System (TCSS), Mindful Attention Awareness Scale (MAAS), Visual analog scale (VAS), Diabetes Specificity Quality of life Scale (DSQL) and tumor necrosis factor-&#945;. Overall, the addition of mindfulness training to Tai Chi effectively enhances the exercise effects of Tai Chi. Therefore, mindfulness training combined with Tai Chi is worthy of promotion and application.

Author Spotlight: Integrating Tai Chi with Mindfulness Training to Achieve an Effective Mind-Body Exercise 

When studying exercise for treating diabetic peripheral neuropathy (DPN), achieving mind-body exercise is essential. This study proposes a protocol for mindfulness training combined with Tai Chi to achieve mind-body exercise.

Diabetic peripheral neuropathy (DPN) is one of the most prevalent chronic complications of diabetes. One of its crucial therapy approaches is mind-body ...

Establishment of the KOA Model in Rabbits Using the Modified Videman Method

Application of Acupotomy in a Knee Osteoarthritis Model in Rabbit

Knee osteoarthritis (KOA) is one of the most frequently encountered diseases in the orthopedic department, which seriously reduces the quality of life of people with KOA. Among several pathogenic factors, the biomechanical imbalance of the knee joint is one of the main causes of KOA. Acupotomology believes that restoring the mechanical balance of the knee joint is the key to treating KOA. Clinical studies have shown that acupotomy can effectively reduce pain and improve knee mobility by reducing adhesion, contracture of soft tissues, and stress concentration points in muscles and tendons around the knee joint. 
In this protocol, we used the modified Videman method to establish a KOA model by immobilizing the left hindlimb in a straight position. We have outlined the method of operation and the precautions related to acupotomy in detail and evaluated the efficacy of acupotomy in conjunction with the theory of "Modulating Muscles and Tendons to Treat Bone Disorders" through the detection of the mechanical properties of quadriceps femoris and tendon, as well as cartilage mechanics and morphology. The results show that acupotomy has a protective effect on cartilage by adjusting the mechanical properties of the soft tissues around the knee joint, improving the cartilage stress environment, and delaying cartilage degeneration.

Author Spotlight: Investigating the Mechanism of Action of Acupotomy in Treating Knee Osteoarthritis

In this protocol, a knee osteoarthritis model was prepared using the modified Videman method, and the operation procedures and precautions of acupotomy are detailed. The effectiveness of acupotomy has been demonstrated by testing the mechanical properties of quadriceps femoris and tendon and the mechanical and morphological properties of cartilage.

Knee osteoarthritis (KOA) is one of the most frequently encountered diseases in the orthopedic department, which seriously reduces the quality of life of ...

Enhancing Stroke Rehabilitation with Virtual Reality-Based Occupational Training

Cognitive Function and Upper Limb Rehabilitation Training Post-Stroke Using a Digital Occupational Training System

Stroke rehabilitation often requires frequent and intensive therapy to improve functional recovery. Virtual reality (VR) technology has shown the potential to meet these demands by providing engaging and motivating therapy options. The digital occupational training system is a VR application that utilizes cutting-edge technologies, including multi-touch screens, virtual reality, and human-computer interaction, to offer diverse training techniques for advanced cognitive capacity and hand-eye coordination abilities. The objective of this study was to assess the effectiveness of this program in enhancing cognitive function and upper extremity rehabilitation in stroke patients. The training and assessment consist of five cognitive modules covering perception, attention, memory, logical reasoning, and calculation, along with hand-eye coordination training. This research indicates that after eight weeks of training, the digital occupational training system can significantly improve cognitive function, daily living skills, attention, and self-care abilities in stroke patients. This software can be employed as a time-saving and clinically effective rehabilitation aid to complement traditional one-on-one occupational therapy sessions. In summary, the digital occupational training system shows promise and offers potential financial benefits as a tool to support the functional recovery of stroke patients.

Author Spotlight: Rehabilitation of Stroke Patients With a Digital Occupational Training System

The current protocol outlines how the VR-based digital occupational training system enhances the rehabilitation of patients with cognitive impairment and upper limb dysfunction following a stroke.

Stroke rehabilitation often requires frequent and intensive therapy to improve functional recovery. Virtual reality (VR) technology has shown the ...

Diagnosis and Strain Identification of pSS-Related Oral &lt;i&gt;Candida&lt;/i&gt;

Examination of Oral Candida Infection in Primary Sj&#246;gren&#39;s Syndrome Patients

Primary Sj&#246;gren's syndrome (pSS) is an autoimmune disease characterized by symptoms such as dry mouth, dry eyes, and other systematic symptoms. Due to the hyposalivation experienced by pSS patients, oral dysbacteriosis often occurs. A common complication of pSS is the oral Candida infection. In this article, the authors describe systematic methods that can effectively diagnose oral Candida infection and identify the Candida strains using saliva, oral mucosal swabs, or mouthwash from pSS patients. The Sabouraud's Dextrose Agar (SDA), hyphal formation assay, potassium hydroxide (KOH) smear test, and calcofluor white (CFW) staining assay are used for the diagnosis of oral Candida infection. A Candida diagnostic agar is used for the identification of Candida strains. Finally, antifungal susceptibility testing is used to determine appropriate antifungal drug treatment. This standardized method can enhance the diagnosis, treatment, and future research of pSS-related oral Candida infections. Early diagnosis, using this method, can also prevent any complications arising due to delay in receiving appropriate treatment.

Author Spotlight: Oral &lt;i&gt;Candida&lt;/i&gt; Diagnosis to Advance Clinical Treatment Regimen for pSS Patients

Here, we present a protocol for the examination of oral Candida infection in patients with primary Sj&#246;gren's syndrome, which can be used for timely treatment and, thereafter, avoiding related complications.

Primary Sj&#246;gren's syndrome (pSS) is an autoimmune disease characterized by symptoms such as dry mouth, dry eyes, and other systematic symptoms. Due ...

Standardizing Press Needle Treatment for Myopia with Dry Eye

Press Needle: A Traditional Chinese Medicine Therapy for Myopia Patients with Dry Eye

Most patients with myopia have dry eye, which has been shown to adversely affect ocular symptoms, myopia progression, and quality of life in patients with myopia. Needle prickling has been shown to be effective in providing symptom relief in patients with myopia and dry eye. Press needle is a long-lasting, easy-to-operate, and inexpensive traditional Chinese medicine treatment. The standard practice of needle insertion is very important for the treatment of myopia and dry eye. The specific steps include selecting the appropriate acupoints, piercing them with appropriate needles, and fixing them in the skin or subcutaneously at the acupoints, burying them for 2 days, resting for 1 day; the course of treatment lasts for 2 weeks. Specifically, the following indicators were assessed: uncorrected visual acuity and the ocular surface disease index. This article will explain how to standardize the operation of a press needle in the treatment of myopia and dry eye.

Author Spotlight: Exploring Press Needle Efficacy and Underlying Molecular Pathways

Here, we present a protocol to standardize the operation of acupuncture in the treatment of myopia with dry eye.

Most patients with myopia have dry eye, which has been shown to adversely affect ocular symptoms, myopia progression, and quality of life in patients with ...

Assessing Sleep Quality and Cognitive Function in Patients with Major Depressive Disorder

Association Between Sleep Quality and Cognitive Symptoms in Patients with Major Depressive Disorder

Cognitive symptoms and sleep disturbance (SD) are common non-mood-related symptoms of major depressive disorder (MDD). In clinical practice, both cognitive symptoms and SD are related to MDD progression. However, there are only a few studies investigating the connection between cognitive symptoms and SD in patients with MDD, and only preliminary evidence suggests a significant association between cognitive symptoms and SD in patients with mood disorders. This study investigates the relationship between cognitive symptoms and sleep quality in patients with major depressive disorder. Patients (n = 20) with MDD were enrolled; their mean Hamilton Depression Scale-17 score was 21.95 (&plusmn;2.76). Gold standard polysomnography (PSG) was used to assess sleep quality, and the validated THINC-integrated tool (the cognitive screening tool) was used to evaluate cognitive function in MDD patients. Overall, the results showed significant correlations between the cognitive screening tool's total score and sleep latency, wake-after-sleep onset, and sleep efficiency. These findings indicate that cognitive symptoms are associated with poor sleep quality among patients with MDD.

Author Spotlight: Unveiling the Connection Between Sleep Disorders and Cognitive Symptoms in Depression

Here, we present a protocol that investigates the relationship between cognitive symptoms and sleep quality in patients with major depressive disorder. The THINC-integrated tool and polysomnography were used to evaluate cognitive symptoms and sleep quality.

Cognitive symptoms and sleep disturbance (SD) are common non-mood-related symptoms of major depressive disorder (MDD). In clinical practice, both ...

Rehabilitation of Patient Cognitive Dysfunction Using a Digital Training System

To begin, position the patient in front of the digital occupational training system, adjust the instrument's display to the appropriate height and tilt angle, allowing the patient to touch the screen. Select the appropriate training program based on the patient's cognitive impairment and muscle strength. Then set the parameters, such as training duration, difficulty level, and side for each program.For rapid matching training, click on Pictures on the screen and ask the patient to remember the pictures shown. Click the icon button to confirm if the shown picture matches the previous one. For memory matrix training, click to make three bright squares flash at different locations on the screen matrix.Then click to darken all squares and ask the patient to click on the bright squares. To train the patient's reaction ability, instruct the patient to click on the catch icon when the cake falls above the cartoon avatar to prevent the cake from hitting the head. To train the color match ability, guide the patient to click on the corresponding color of a ball when it is close to the center of the circle.This will make the ball bounce either two or four times. Next, train the patient's reactive ability by asking the patient to click and hit the bad guy or gopher when it sticks its head out. For memory training, display information of cards on the screen.Now, flip the card and change its position. Ask the patient to find and click on the target card. To train the patient's judgment, display a left and right hand gesture on the screen.Ask the patient to determine which hand wins or if it is a tie. Perform arithmetic reasoning training by instructing the patient to calculate the arithmetic problem on the screen and compare it to the number. Ask the patient to select the appropriate button corresponding to greater than, less than, or equal to.Train the patient in sorting and picking by instructing the patient to pick and click on the appropriate type and item quantity from the list provided. Additionally, train the patient's judgment by asking the patient to click and capture a specific type and number of fish. For unilateral neglect training, ask the patient to click according to the video prompts to control the swimming red fish and consume as many fish as possible.Next, train the patients with a jigsaw puzzle by clicking on the broken puzzle pieces to reposition them correctly. Finally, perform picture combination training by choosing the appropriate pictures from various shapes and colors on the left side of the screen and placing them in the correct order on the right side of the screen to form a specific pattern. For patients with executive dysfunction, train them with the following programs.For food preparation, instruct the patient to virtually turn on the faucet, clean the tomatoes, and cut them into pieces. Next, place the cutup tomatoes onto a plate. Place the eggs into the bowl and stir them together.Instruct the patient to fire up the stove, pour the cooking oil, beaten eggs, and then the tomatoes. Once cooking is complete, guide the patient to turn off the heat and transfer the cooked dish onto a plate. Train the patients with thinking and reasoning dysfunction with naming, card memory, and object differentiation programs.For naming training, guide the patients to find and click on the correct picture or item name based on the information and sound prompts. For the card memory training, ask the patient to find and click the card that is the same as the one in the hand of the cartoon avatar in the upper right corner. To train the patient in object differentiation, identify and click on the object that is unique and different from the remaining objects.To perform upper limb functional training, ask the patient to draw specific pattern lines according to the path prompts on the screen. Train the patient in musical recognition by erasing the gray squares in sync with the music rhythm, transforming them into colorful squares. For walking the maze, ask the patient to hold onto the small ball in the maze and navigate the maze to reach the diamond at the maze's end.Finally, train the patients for two-handed coordination using the given programs. For the balance ball training, have the patient place their left and right fists on both ends of the balance beam with a ball on it. Instruct the patient to maintain the ball's balance on the beam.To play the fish feeding game, instruct the patient to hold down the feed with one hand and click the small fish on the screen with the other hand. Next, guide the patient for archery practice by making the patient place one hand on the bow and the other on the arrow. Click control the arrow to release it and hit the target.Finally, train the reaction coordination of the patient by instructing the patient to hold the hammer down using both hands, then click to hit the yellow ball alternately. Patients that underwent rehabilitation with a digital occupational system displayed greater improvements relative to the conventional system.