Cognitive screening test for rehabilitation using spatiotemporal data extracted from a digital trail making test part-A.

We investigated a newly developed digitized Trail Making Test using an iPad (iTMT) as a brief cognitive function screening test. We found that the iTMT part-A (iTMT-A) can estimate generalized cognitive function in rehabilitation inpatients examined using the Mini-Mental State Examination (MMSE). Forty-two hospitalized participants undergoing rehabilitation (rehab participants), 30 of whom had cerebral infarction/hemorrhage (stroke participants), performed the iTMT five times (first three times: iTMT-A; fourth: paper version of TMT-A; fifth: the inverse version of iTMT-A) and the MMSE once. Each iTMT-A trial's completion time was divided into the move and dwell times. A linear mixed model following post-hoc tests revealed that the completion time of the third and fourth iTMT-A was faster compared to that of the first iTMT-A, suggesting the presence of a learning effect. In the partial least squares (PLS) regression analysis, the coefficient of determination for estimating the MMSE score was increased by using the dwell and move times extracted from the repeated iTMT-A and the availability of TMT-B, even for subjects with low MMSE scores. These findings indicate that the dwell time of iTMT-A may be important for estimating cognitive function. The iTMT-A extracts significant factors temporally and spatially, and by incorporating the learning effect of repeated trials, it may be possible to screen cognitive and physical functions for rehabilitation patients.

Vertical dynamic visual acuity is significantly lower than horizontal dynamic visual acuity.

Dynamic visual acuity (DVA) is crucial for the perception of moving objects. While traditional DVA assessment tools predominantly focus on horizontal movements, the evaluation of vertical DVA remains unstandardized. Consequently, the disparities between vertical and horizontal DVAs are yet to be thoroughly investigated. Therefore, we designed a system capable of conducting multidirectional DVA tests and eye movement measurements. During the experiments, the participants identified the gap direction of the Landolt-C ring moving either horizontally or vertically. The speed of movement decelerated from its maximum as a high-speed infrared camera captured the pupil movements of the left eye at 500 fps. We conducted tests on 15 healthy university students (aged [Formula: see text] years) and measured vertical and horizontal DVAs five times each. DVA was deduced from the Landolt-C ring speed with accurate gap direction responses, and eye movement was assessed based on the total gaze movement distance. The results revealed superior DVA and eye movement in the horizontal direction compared with the vertical direction ([Formula: see text]). This highlights the anisotropic characteristics of DVA and eye movement. The proposed system has the potential for multidirectional dynamic vision evaluation and training in clinical scenarios.

Clinical utility of paced finger tapping assessment in idiopathic normal pressure hydrocephalus.

Background: The Finger Tapping (F-T) test is useful for assessing motor function of the upper limbs in patients with idiopathic normal pressure hydrocephalus (iNPH). However, quantitative evaluation of F-T for iNPH has not yet been established. The purpose of this study was to investigate the usefulness of the quantitative F-T test and optimal measurement conditions as a motor evaluation and screening test for iNPH. Methods: Sixteen age-matched healthy controls (mean age 73 ± 5 years; 7/16 male) and fifteen participants with a diagnosis of definitive iNPH (mean age 76 ± 5 years; 8/15 male) completed the study (mean ± standard deviation). F-T performance of the index finger and thumb was quantified using a magnetic sensing device. The performance of repetitive F-T by participants was recorded in both not timing-regulated and timing-regulated conditions. The mean value of the maximum amplitude of F-T was defined as M-Amplitude, and the mean value of the maximum velocity of closure of F-T was defined as cl-Velocity. Results: Finger Tapping in the iNPH group, with or without timing control, showed a decrease in M-Amplitude and cl-Velocity compared to the control group. We found the only paced F-T with 2.0 Hz auditory stimuli was found to improve both M-Amplitude and cl-Velocity after shunt surgery. Conclusion: The quantitative assessment of F-T with auditory stimuli at the rate of 2.0 Hz may be a useful and potentially supplemental screening method for motor assessment in patients with iNPH.

Finger Tapping Test for Assessing the Risk of Mild Cognitive Impairment.

Aim: A testing method for early diagnosis of Mild cognitive dementia (MCI) that can be easily applied in clinical practice was investigated in this study. We examined whether MCI risk can be determined through finger movements. Methods: Between 2013 and 2020, 1097 individuals were screened. After applying propensity-score matching to adjust for variability between the groups, 173 individuals each in the mild cognitive impairment and control groups were selected. Thereafter, differences between groups in mean values of parameters extracted from finger tap movements were determined using unpaired t-test and effect size. Furthermore, area under the curve, sensitivity, and specificity were calculated from the receiver operating characteristic curve for parameters with significant difference. Results: A significant difference was observed, especially in the number of taps in the MCI group compared with that in the control group (p < .001; 95% CI, -12.7 to -8.8; r = 0.51). A cut-off value of 30 taps was applied (sensitivity, 0.77; specificity, 0.67; AUC, 0.79). Significant differences were also observed in rhythm-related parameters. Conclusions: These parameters might be useful for capturing MCI risk. Finger taps are easily measured and may be suitable for screening large populations. This tool might be used as a supplemental method to increase the sensitivity of traditional cognitive tests.

Hemodynamic response to intestinal pH stimulation measured with spectroscopic video imaging.

To investigate the relationship between the gut and skin (gut-skin axis), head skin hemodynamic responses to gut stimulation including the injection of acetic acid in nude mice were measured by spectroscopic video imaging, which was calculated using a modified Beer-Lambert formula. The relationship with blood proteins was also analyzed. The blood volume changes in three mice injected with acetic acid were highly reproducible in the mathematical model equation. Four proteins correlated with blood volume changes were all related to immunity. These results suggest that intestinal pH can alter the blood volume in the skin and induce immune-related responses.

Impaired sharp-wave ripple coordination between the medial entorhinal cortex and hippocampal CA1 of knock-in model of Alzheimer's disease.

Clinical evidence suggests that the entorhinal cortex is a primary brain area triggering memory impairments in Alzheimer's disease (AD), but the underlying brain circuit mechanisms remain largely unclear. In healthy brains, sharp-wave ripples (SWRs) in the hippocampus and entorhinal cortex play a critical role in memory consolidation. We tested SWRs in the MEC layers 2/3 of awake amyloid precursor protein knock-in (APP-KI) mice, recorded simultaneously with SWRs in the hippocampal CA1. We found that MEC→CA1 coordination of SWRs, found previously in healthy brains, was disrupted in APP-KI mice even at a young age before the emergence of spatial memory impairments. Intriguingly, long-duration SWRs critical for memory consolidation were mildly diminished in CA1, although SWR density and amplitude remained intact. Our results point to SWR incoordination in the entorhinal-hippocampal circuit as an early network symptom that precedes memory impairment in AD.

Artificially-reconstructed brain images with stroke lesions from non-imaging data: modeling in categorized patients based on lesion occurrence and sparsity.

Brain imaging is necessary for understanding disease symptoms, including stroke. However, frequent imaging procedures encounter practical limitations. Estimating the brain information (e.g., lesions) without imaging sessions is beneficial for this scenario. Prospective estimating variables are non-imaging data collected from standard tests. Therefore, the current study aims to examine the variable feasibility for modelling lesion locations. Heterogeneous variables were employed in the multivariate logistic regression. Furthermore, patients were categorized (i.e., unsupervised clustering through k-means method) by the charasteristics of lesion occurrence (i.e., ratio between the lesioned and total regions) and sparsity (i.e., density measure of lesion occurrences across regions). Considering those charasteristics in models improved estimation performances. Lesions (116 regions in Automated Anatomical Labeling) were adequately predicted (sensitivity: 80.0-87.5% in median). We confirmed that the usability of models was extendable to different resolution levels in the brain region of interest (e.g., lobes, hemispheres). Patients' charateristics (i.e., occurrence and sparsity) might also be explained by the non-imaging data as well. Advantages of the current approach can be experienced by any patients (i.e., with or without imaging sessions) in any clinical facilities (i.e., with or without imaging instrumentation).

Projection of Damaged Visual and Language Regions on Low Trail Making Test Part-B Performance in Stroke Patients.

Background: The Trail Making Test Part-B (TMT-B) is an attention functional test to investigate cognitive dysfunction. It requires the ability to recognize not only numbers but also letters. We analyzed the relationship between brain lesions in stroke patients and their TMT-B performance. Methods: From the TMT-B, two parameters (score and completion time) were obtained. The subjects were classified into several relevant groups by their scores and completion times through a data-driven analysis (k-means clustering). The score-classified groups were characterized by low (≤10), moderate (10 < score < 25), and high (25) scores. In terms of the completion time, the subjects were classified into four groups. The lesion degree in the brain was calculated for each of the 116 regions classified by automated anatomical labeling (AAL). For each group, brain sites with a significant difference (corrected p < 0.1) between each of the 116 regions were determined by a Wilcoxon Rank-Sum significant difference test. Results: Lesions at the cuneus and the superior occipital gyrus, which are mostly involved in visual processing, were significant (corrected p < 0.1) in the low-score group. Furthermore, the moderate-score group showed more-severe lesion degrees (corrected p < 0.05) in the regions responsible for the linguistic functions, such as the superior temporal gyrus and the supramarginal gyrus. As for the completion times, lesions in the calcarine, the cuneus, and related regions were significant (corrected p < 0.1) in the fastest group as compared to the slowest group. These regions are also involved in visual processing. Conclusion: The TMT-B results revealed that the subjects in the low-score group or the slowest- group mainly had damage in the visual area, whereas the subjects in the moderate-score group mainly had damage in the language area. These results suggest the potential utility of TMT-B performance in the lesion site.

Increased cerebrovascular reactivity in selected brain regions after extracranial-intracranial bypass improves the speed and accuracy of visual cancellation in patients with severe steno-occlusive disease: a preliminary study.

The effect of the change in cerebrovascular reactivity (CVR) in each brain area on cognitive function after extracranial-intracranial bypass (EC-IC bypass) was examined. Eighteen patients who underwent EC-IC bypass for severe unilateral steno-occlusive disease were included. Single-photon emission CT (SPECT) for evaluating CVR and the visual cancellation (VC) task were performed before and after surgery. The accuracy of VC was expressed by the arithmetic mean of the age-matched correct answer rate and the accurate answer rate, and the averages of the time (time score) and accuracy (accuracy score) of the four VC subtests were used. The speed of VC tended to be slower, whereas accuracy was maintained before surgery. The EC-IC bypass improved CVR mainly in the cerebral hemisphere on the surgical side. On bivariate analysis, when CVR increased post-operatively, accuracy improved on both surgical sides, but the time score was faster on the left and slower on the right surgical side. Stepwise multiple regression analysis showed that the number of the brain regions associated with the time score was 5 and that associated with the accuracy score was 4. In the hemodynamically ischemic brain, processing speed might be adjusted so that accuracy would be maintained based on the speed-accuracy trade-off mechanism that may become engaged separately in the left and right cerebral hemispheres when performing VC. When considering the treatment for hemodynamic ischemia, the relationship between CVR change and the speed-accuracy trade-off in each brain region should be considered.

Boys with attention-deficit/hyperactivity disorder perform wider and fewer finger tapping than typically developing boys - Peer comparisons and the effects of methylphenidate from an exploratory perspective.

AIM: This study aimed to investigate the differences in fine motor and coordination skills between boys with attention-deficit/hyperactivity disorder (ADHD) and typically developing (TD) boys and the effect of methylphenidate (MPH) in boys with ADHD. METHODS: Fourteen boys aged 7-12 years who were diagnosed with ADHD and previously treated with MPH were instructed to tap their thumbs and index fingers together repetitively for 10 s after attaching magnetic sensors. The participants executed "in-phase" and "anti-phase" tapping. A two-way analysis of variance for comparing boys with ADHD and TD boys and the paired t-test to investigate the effect of MPH between sessions with and without MPH were performed. RESULTS: Boys with ADHD showed a significantly lower "number of taps" and a significantly higher "average of local maximum distance" than TD boys. "Energy balance" was significantly lower in ADHD boys than in TD boys. MPH caused a significant difference in the "standard deviation (SD) of phase difference" in "anti-phase tapping." CONCLUSION: Our studies indicated that finger-tapping movements in boys with ADHD tended to be significantly wider and fewer than those in TD boys, and MPH may improve the phase difference of bimanual fine motor coordination skills in boys with ADHD who are above 1.0 SD. The results should be interpreted with caution because we conducted statistical tests for many outcomes and groups without considering the multiplicity factor from an exploratory perspective.

Pen-point Trajectory Analysis During Trail Making Test Based on a Time Base Generator Model.

The Trail Making test (TMT) is a widely used neuropsychological test to assess the cognitive function of patients. This paper presents the analysis method of pen-point trajectory during the TMT based on a time base generator (TBG). In the proposed method, the movement segments between targets are first extracted from pen-point trajectories, which are measured during performance of the TMT on an iPad. By fitting the extracted trajectories with a TBG-based trajectory generation model, the proposed method can then calculate quantitative indices representing the shape and collapse of the velocity profile. In the experiment, we analyzed TMT data from 25 stroke patients who were classified into three groups according to their scores on the Mini-Mental State Examination (MMSE). The results revealed that most of the measured inter-target trajectories had unimodal bell-shaped velocity profiles, as seen in reaching movements. Furthermore, we found that the degree of collapse in the velocity profile shape increased significantly when the cognitive function decreased.

Early Identification of Alzheimer's Disease in Mouse Models: Application of Deep Neural Network Algorithm to Cognitive Behavioral Parameters.

Alzheimer's disease (AD) is a worldwide burden. Diagnosis is complicated by the fact that AD is asymptomatic at an early stage. Studies using AD-modeled animals offer important and useful insights. Here, we classified mice with a high risk of AD at a preclinical stage by using only their behaviors. Wild-type and knock-in AD-modeled (App NL-G-F/NL-G-F ) mice were raised, and their cognitive behaviors were assessed in an automated monitoring system. The classification utilized a machine learning method, i.e., a deep neural network, together with optimized stepwise feature selection and cross-validation. The AD risk could be identified on the basis of compulsive and learning behaviors (89.3% ± 9.8% accuracy) shown by AD-modeled mice in the early age (i.e., 8-12 months old) when the AD symptomatic cognitions were relatively underdeveloped. This finding reveals the advantage of machine learning in unveiling the importance of compulsive and learning behaviors for early AD diagnosis in mice.

Assessment of finger motor function that reflects the severity of cognitive function.

OBJECTIVES: We conducted a finger tapping movement test using a finger tapping device with magnetic sensors (UB-2) and performed multiple regression analyses using a number of finger movements parameters to estimate the severity of cognitive impairment. METHODS: The subjects of this study were 64 patients, including 44 diagnosed with Alzheimer's disease (AD) (mean age: 73.8±7.0 years) and 20 diagnosed with mild cognitive impairment (MCI) (mean age: 76.7±4.2 years). For the finger-tapping movement tasks, we tested single-hand (left and right) tapping, simultaneous tapping of both hands, and alternate tapping between hands. After measurement, multiple regression analysis adjusted for age and sex was performed to predict the Mini-Mental State Examination (MMSE) score from the calculated hand parameters. RESULTS: Relatively high standardized partial regression coefficients were observed for the following two parameters: standard deviation (SD) of distance rate of velocity peak in extending movement and the SD of contact duration. The coefficients of determination (R2) ranged between 0.1 to 0.28. CONCLUSIONS: Our results suggest the possibility that these parameters may be used to assess cognitive function. We shall obtain large-scale data from older people to examine the possibility of these parameters to be used as an early diagnostic tool for dementia patients.

Lesions in the right Rolandic operculum are associated with self-rating affective and apathetic depressive symptoms for post-stroke patients.

Stroke survivors majorly suffered from post-stroke depression (PSD). The PSD diagnosis is commonly performed based on the clinical cut-off for psychometric inventories. However, we hypothesized that PSD involves spectrum symptoms (e.g., apathy, depression, anxiety, and stress domains) and severity levels. Therefore, instead of using the clinical cut-off, we suggested a data-driven analysis to interpret patient spectrum conditions. The patients' psychological conditions were categorized in an unsupervised manner using the k-means clustering method, and the relationships between psychological conditions and quantitative lesion degrees were evaluated. This study involved one hundred sixty-five patient data; all patients were able to understand and perform self-rating psychological conditions (i.e., no aphasia). Four severity levels-low, low-to-moderate, moderate-to-high, and high-were observed for each combination of two psychological domains. Patients with worse conditions showed the significantly greater lesion degree at the right Rolandic operculum (part of Brodmann area 43). The dissimilarities between stress and other domains were also suggested. Patients with high stress were specifically associated with lesions in the left thalamus. Impaired emotion processing and stress-affected functions have been frequently related to those lesion regions. Those lesions were also robust and localized, suggesting the possibility of an objective for predicting psychological conditions from brain lesions.

Quantitative assessment of fine motor skills in children using magnetic sensors.

AIM: We aimed to establish objective and quantitative data on fine motor development in typically developing children using magnetic sensors. METHODS: The study included 110 Japanese elementary school children volunteers (57 boys, 53 girls). The participants were instructed to tap their thumbs and index fingers together repetitively for 10 s. After attaching coils to the participants' right and left thumbs and index fingers, participants executed "in-phase" and "anti-phase" tapping. We used two-way analysis of variance to analyze the influences of age and sex on fine motor development. RESULTS: The "number of taps" significantly increased with age, while the "standard deviation (SD) of tapping interval" significantly decreased. More than half of the "acceleration" parameters significantly increased with age. Boys performed significantly faster than girls in some parameters of "velocity" and "acceleration," while girls had significantly lower "SD of local maximum velocity in opening motion" and "SD of local minimum velocity in closing motion." DISCUSSION: We established both objective and quantitative reference data on fine motor development in typically developing Japanese children aged between 7 and 12 years using magnetic sensors. We revealed that this system can monitor real-time details of the parameters involved in the finger-tapping movement in children without complications. This device could be useful for obtaining objective and quantitative data on fine motor skills in the clinical assessment of developmental coordination disorder, assessments of educational intervention, or rehabilitation and discovery of new therapeutic agents.

Noninvasive Mapping of Premature Ventricular Contractions by Merging Magnetocardiography and Computed Tomography.

OBJECTIVES: This study aimed to develop a novel premature ventricular contraction (PVC) mapping method to predict PVC origins in whole ventricles by merging a magnetocardiography (MCG) image with a cardiac computed tomography (CT) image. BACKGROUND: MCG can noninvasively discriminate PVCs originating from the aortic sinus cusp from those originating from the right ventricular outflow tract. METHODS: This study was composed of 22 candidates referred for catheter ablation of idiopathic PVCs. MCG and CT were performed the same day before ablation. Estimated origins by MCG-CT imaging using the recursive null steering spatial filter algorithm were compared with origins determined by electroanatomic mapping (CARTO, Biosense Webster, Inc., Diamond Bar, California) during the ablation procedure. Radiopaque acrylic markers for the CT scan and coil markers generating a weak magnetic field during MCG measurements were used as reference markers to merge the 2 images 3-dimensionally. RESULTS: PVC origins were determined by endocardial and epicardial mapping and ablation results in 18 (86%) patients (right ventricular outflow tract in 10 patients, aortic sinus cusp in 2 patients, interventricular septum in 1 patient, near His bundle in 1 patient, right ventricular free wall in 1 patient, and left ventricular free wall in 3 patients). Estimated origins by MCG-CT imaging matched the origins determined during the procedure in 94% (17 of 18) of patients, whereas the electrocardiography algorithms were accurate in only 56% (10 of 18). Discrimination of an epicardium versus an endocardium or right- versus left-sided septum was successful in 3 of 4 patients (75%). CONCLUSIONS: The diagnostic accuracy of noninvasive MCG-CT mapping was high enough to allow clinical use to predict the site of PVC origins in the whole ventricles.

Nigrostriatal Dopaminergic Dysfunction and Altered Functional Connectivity in REM Sleep Behavior Disorder With Mild Motor Impairment.

Rapid eye movement sleep behavior disorder is parasomnia characterized by symptoms of dream enactment and loss of muscle atonia during rapid eye movement sleep. Mild motor impairment is present in some patients with rapid eye movement sleep behavior disorder and presumed to be a risk factor for conversion to synucleinopathies. The purpose of this study is to identify patients with mild motor impairment by evaluating finger tapping and to investigate its pathophysiology. Twenty-three patients with rapid eye movement sleep behavior disorder and 20 healthy control subjects were recruited in the present study. We accurately evaluated finger tapping including amplitude, peak open, and close speed with a magnetic sensing device and identified patients with mild motor impairment. Moreover, we performed 123I-2ß-carbomethoxy-3ß-(4-iodophenyl) nortropane SPECT and resting state functional MRI. 123I-2ß-carbomethoxy-3ß-(4-iodophenyl) nortropane uptake for each bilateral caudate, anterior putamen, and posterior putamen was calculated and the resting state functional connectivity of sensorimotor network was analyzed. Using finger tapping parameters, we identified eight patients with mild motor impairment. In patients with mild motor impairment, all finger tapping parameters were significantly impaired when compared to patients with normal motor function, while they exhibited no significant differences in Unified Parkinson's Disease Rating Scale part III score. 123I-2ß-carbomethoxy-3ß-(4-iodophenyl) nortropane uptake in the right posterior putamen, bilateral anterior putamen, and caudate was significantly lower when compared to healthy controls or patients with rapid eye movement sleep behavior disorder with normal motor function. These patients also exhibited decreased cortico-striatal functional connectivity and increased cortico-cerebellar functional connectivity when compared to healthy controls or patients with normal motor function. Our results show that mild motor impairment in rapid eye movement sleep behavior disorder evaluated by finger tapping task presented mild nigrostriatal dopaminergic dysfunction as well as alterations in resting state sensorimotor network. Although longitudinal follow up is necessary, such patients may have higher risk of short-term conversion to synucleinopathies.

Detection of Abnormal Segments in Finger Tapping Waveform using One-class SVM.

We have developed a finger-tapping device with magnetic sensors, UB2, for the early detection of dementia. The goal of the present study is to develop a method for detecting abnormal segments in the finger tapping waveform in an objective way using machine learning and to evaluate the method in comparison with a human visual assessment. Fifteen-second right-hand finger tapping waveforms of 228 healthy volunteers were measured and cut into one-cycle taps. Fifteen features representing the properties of the one-cycle taps were extracted. As a result of applying a one-class support vector machine (SVM) with an outlier rate of 0.08, 1032 one-cycle taps (8.0%) were detected as abnormal among all 12,898 one-cycle taps. Among these abnormal ones, the features including many outliers (>30%) were the instances of freezing (small fluctuations) and the tap interval. These features correspond to those of which distribution were markedly biased. The visual assessment was likely to overestimate abnormality concerning the instances of freezing and the tap interval (>10%) and conversely underestimate abnormality concerning amplitude of distance/velocity or motion quantity (<; -10%).