Motor flexibility to stabilize the toe position during obstacle crossing in older adults: an investigation using an uncontrolled manifold analysis.

Introduction: An age-related decrease in the ability to exploit the abundant degrees of freedom of the body, referred to as motor flexibility, leads to a heightened fall risk. The present study investigated motor flexibility to stabilize the toe position during obstacle crossing in older adults and its correlation with the magnitude of foot elevation. Methods: Twenty-six older adults (70.9 ± 7.4 years old) and 21 younger adults (25.4 ± 5.0 years old) walked and crossed an obstacle, during which the dominant limb was always the leading limb. An uncontrolled manifold (UCM) analysis was used to quantify the flexibility during obstacle crossing as the synergy index, with the vertical toe position being regarded as the performance variable and the segment angles of the lower limbs as the elemental variables. Results and discussion: The results showed that older participants had a significantly lower synergy index for the trailing limb before the moment of obstacle crossing than younger participants, suggesting reduced flexibility in part. The results also showed that, regardless of age, foot elevation was negatively correlated with the synergy index, suggesting that a so-called "conservative strategy" (i.e., a tendency to show extraordinarily high foot elevation to ensure collision avoidance) may be related to their reduced motor flexibility.

Cancer-specific cytotoxicity of Ringer's acetate solution irradiated by cold atmospheric pressure plasma.

Cold atmospheric pressure plasmas are promising medical tools that can assist in cancer treatment. While the medical pathology mechanism is substantially understood, knowledge of the contribution of reactive species formed in plasma and the mode of activation of biochemical pathways is insufficient. Herein, we present a concept involving antitumoral plasma-activated organics, which is envisaged to increase cytotoxicity levels against cancer cells. Ringer's acetate solution was irradiated by low-temperature plasma at atmospheric pressure and possible reaction pathways of the compound generation are presented. The chemical compounds formed by plasma treatment and their effects on non-tumorigenic breast epithelial cells (MCF-10A) and breast cancer cells (MCF-7) were investigated. The cell viability results have shown that plasma-derived compounds have both, stimulatory and inhibitory effects on cell viability, depending on the concentration of the generated compounds in the irradiated liquids. Previous studies have shown that oxidative stresses involving reactive oxygen and nitrogen species (RONS) can be used to kill cancer cells. Hence, while RONS offers promising first-step killing effects, cell viability results have shown that plasma-derived compounds, such as acetic anhydride and ethyl acetate, have the potential to play important roles in plasma-based cancer therapy.

The NMDA receptor antagonist ketamine impairs and delays context-dependent decision making in the parietal cortex.

Flexible decision making is an indispensable ability for humans. A subanesthetic dose of ketamine, an N-methyl-D-aspartate receptor antagonist, impairs this flexibility in a manner that is similar to patients with schizophrenia; however how it affects neural processes related to decision making remains unclear. Here, we report that ketamine administration impairs neural processing related to context-dependent decision making, and delays the onset of decision making. We recorded single unit activity in the lateral intraparietal area (LIP) while monkeys switched between a direction-discrimination task and a depth-discrimination task. Ketamine impaired choice accuracy for incongruent stimuli that required different decisions depending on the task, for the direction-discrimination task. Neural sensitivity to irrelevant depth information increased with ketamine during direction discrimination in LIP, indicating impaired processing of irrelevant information. Furthermore, the onset of decision-related neural activity was delayed in conjunction with an increased reaction time irrespective of task and stimulus congruency. Neural sensitivity and response onset of the middle temporal area (MT) were not modulated by ketamine, indicating that ketamine worked on neural decision processes downstream of MT. These results suggest that ketamine administration may impair what information to process and when to process it for the purpose of achieving flexible decision making.

Prediction-Related Frontal-Temporal Network for Omission Mismatch Activity in the Macaque Monkey.

Sensory prediction is considered an important element of mismatch negativity (MMN) whose reduction is well known in patients with schizophrenia. Omission MMN is a variant of the MMN which is elicited by the absence of a tone previously sequentially presented. Omission MMN can eliminate the effects of sound differences in typical oddball paradigms and affords the opportunity to identify prediction-related signals in the brain. Auditory predictions are thought to reflect bottom-up and top-down processing within hierarchically organized auditory areas. However, the communications between the various subregions of the auditory cortex and the prefrontal cortex that generate and communicate sensory prediction-related signals remain poorly understood. To explore how the frontal and temporal cortices communicate for the generation and propagation of such signals, we investigated the response in the omission paradigm using electrocorticogram (ECoG) electrodes implanted in the temporal, lateral prefrontal, and orbitofrontal cortices of macaque monkeys. We recorded ECoG data from three monkeys during the omission paradigm and examined the functional connectivity between the temporal and frontal cortices by calculating phase-locking values (PLVs). This revealed that theta- (4-8 Hz), alpha- (8-12 Hz), and low-beta- (12-25 Hz) band synchronization increased at tone onset between the higher auditory cortex and the frontal pole where an early omission response was observed in the event-related potential (ERP). These synchronizations were absent when the tone was omitted. Conversely, low-beta-band (12-25 Hz) oscillation then became stronger for tone omission than for tone presentation approximately 200 ms after tone onset. The results suggest that auditory input is propagated to the frontal pole via the higher auditory cortex and that a reciprocal network may be involved in the generation of auditory prediction and prediction error. As impairments of prediction may underlie MMN reduction in patients with schizophrenia, an aberrant hierarchical temporal-frontal network might be related to this pathological condition.

Improved Walking Through an Aperture in a Virtual Environment Transfers to a Real Environment: Introduction of Enriched Feedback and Gradual Increase in Task Difficulty.

Virtual reality (VR) could be used to set up a training protocol to improve one's collision-avoidance behavior. In our previous study, we developed a VR system for training older individuals to walk through an aperture in a manner that is both safe (i.e., no collision) and efficient (i.e., no exaggerated behavior to ensure collision avoidance). In the present study, we made several modifications to the VR system in terms of enriched feedback (vibratory stimulation for virtual collisions and the addition of positive feedback for successful trials) and gradual increase in task difficulty during training to strengthen the skill transfer. Nineteen older adults (74.4 ± 5.3 years of age) and 21 younger adults (25.1 ± 5.0 years of age) participated. They were randomly assigned to one of two training groups: the intervention group (older: n = 10; younger: n = 10) or the control group (older: n = 11; younger: n = 9). The experiment consisted of pre- and post-training tests in a real environment and training in a VR environment. During training, participants held a horizontal bar while stepping in place as if a VR image on the screen were moving in response to their stepping. Participants in the intervention group tried to pass a narrow aperture without collision while attempting to minimize their body rotation to avoid collision as much as possible. The criterion upon which the collision-avoidance behavior was regarded as successful became incrementally more demanding as participants successfully met the previous criterion. Participants in the control group passed through a very wide aperture, so that collision-avoidance behavior was unnecessary. A comparison between pre- and post-training test performances showed that, for both older and younger adults in the intervention group, the spatial margins became significantly smaller, while the success rate remained unchanged. For those in the control group, neither the spatial margin nor the success rate was improved. These results suggest that the three modifications made for the VR system contributed to improvement of the system and helped participants transfer the behavior learned from the VR environment to real walking.

Task-specific employment of sensory signals underlies rapid task switching.

Much of our flexible behavior is dependent on responding efficiently to relevant information while discarding irrelevant information. Little is known, however, about how neural pathways governing sensory-motor associations can rapidly switch to accomplish such flexibility. Here, we addressed this question by electrically microstimulating middle temporal (MT) neurons selective for both motion direction and binocular disparity in monkeys switching between direction and depth discrimination tasks. Surprisingly, we frequently found that the observed psychophysical bias precipitated by delivering microstimulation to neurons whose preferred direction and depth were related to opposite choices in the two tasks was substantially shifted toward a specific movement. Furthermore, these effects correlated with behavioral switching performance. Our findings suggest that the outputs of sensory signals are task specific and that irrelevant sensory-motor pathways are gated depending on task demand so as to accomplish rapid attentional switching.

A Single Bout of Constant-Load Exercise Test for Estimating the Time Constant of Oxygen Uptake Kinetics in Individuals With Stroke.

OBJECTIVE: To examine the relationship between the time constant of oxygen uptake kinetics during the onset of exercise (τVO2) estimated from a single exercise bout and that obtained from three averaged exercise bouts in individuals with stroke. METHODS: Twenty participants with stroke performed three bouts of a constant-load pedaling exercise at approximately 80% of the workload corresponding to the ventilatory threshold to estimate τVO2. The VO2 data from the first trial of three bouts were used to estimate τVO2 for a single bout. Additionally, data collected from three bouts were ensemble-averaged to obtain τVO2 for three averaged bouts as the criterion. RESULTS: There was a very high correlation between τVO2 for a single bout (34.8±14.0 seconds) and τVO2 for three averaged bouts (38.5±13.4 seconds) (r=0.926, p<0.001). However, τVO2 for a single bout was smaller than that for three averaged bouts (p=0.006). CONCLUSION: τVO2 for a single bout could reflect the relative difference in τVO2 for three averaged bouts among individuals with stroke. However, it should be noted that τVO2 for a single bout may be underestimated compared to τVO2 for three averaged bouts.

Cardiorespiratory responses to exercise related to post-stroke fatigue severity.

Physical deconditioning after stroke may induce post-stroke fatigue. However, research on this association is limited. Our primary objective was to investigate the associations of post-stroke fatigue severity with oxygen uptake ([Formula: see text]O2) at peak exercise and the time constant of [Formula: see text]O2 kinetics (τ[Formula: see text]O2) at exercise onset. The secondary objective was to examine the associations between fatigue and cardiorespiratory variables potentially affecting [Formula: see text]O2 during exercise. Twenty-three inpatients from a subacute rehabilitation ward were enrolled in this study. The median (interquartile range) Fatigue Severity Scale (FSS) score, as a measure of fatigue, was 32 (range 27-42) points. The FSS score was not associated with [Formula: see text]O2 at peak exercise during a symptom-limited graded exercise test (rho = - 0.264; p = 0.224), whereas it was significantly associated with τ[Formula: see text]O2 during a submaximal constant-load exercise test (rho = 0.530; p = 0.009). A higher FSS score also significantly correlated with a longer time constant of cardiac output (CO) kinetics (rho = 0.476; p = 0.022). Our findings suggest that severe post-stroke fatigue is associated with delayed increases in [Formula: see text]O2 and CO at the onset of exercise. Our findings can contribute to the development of an appropriate rehabilitation programme for individuals with post-stroke fatigue.

Training older adults with virtual reality use to improve collision-avoidance behavior when walking through an aperture.

Many older adults perform collision-avoidance behavior either insufficiently (i.e., frequent collision) or inefficiently (i.e., exaggerated behavior to ensure collision-avoidance). The present study examined whether a training system using virtual reality (VR) simulation enhanced older adults' collision-avoidance behavior in response to a VR image of an aperture during real walking. Twenty-five (n = 13 intervention group and n = 12 control group) older individuals participated. During training, a VR image of walking through an aperture was projected onto a large screen. Participants in the intervention group tried to avoid virtual collision with the minimum body rotation required to walk on the spot through a variety of narrow apertures. Participants in the control group remained without body rotation while walking on the spot through a wide aperture. A comparison between pre-test and post-test performances in the real environment indicated that after the training, significantly smaller body rotation angles were observed in the intervention group. This suggests that the training led participants to modify their behavior to try to move efficiently during real walking. However, although not significant, collision rates also tended to be greater, suggesting that, at least for some participants, the modification required to avoid collision was too difficult. Transfer of the learned behavior using the VR environment to real walking is discussed.

Cardiorespiratory mechanisms underlying the impaired oxygen uptake kinetics at exercise onset after stroke.

BACKGROUND: Oxygen uptake (V˙O2) kinetics at the onset of exercise is slower in patients with stroke than in healthy adults. However, little is known about the cardiorespiratory mechanisms underlying the impaired V˙O2 kinetics. OBJECTIVES: This study aimed to investigate the relative effect of impaired oxygen delivery and utilisation on V˙O2 kinetics at the onset of submaximal exercise in patients with stroke by comparing the time constants of cardiac output (τCO) and V˙O2 (τV˙O2). In addition, we aimed to examine the association between the kinetics of cardiorespiratory variables and functional outcomes. METHODS: We included 21 patients with stroke (15 males, mean [SD] age 58.7 [9.5] years, mean days post-stroke 67.9 [30.9]). A submaximal constant-load exercise test was performed to measure τV˙O2, τCO, and the time constant of arterialvenous oxygen difference (τAVO2diff). The ratio of τCO to τV˙O2 was calculated to assess the matching of oxygen delivery and consumption. Fugl-Meyer lower-extremity motor scores, comfortable gait speeds, and Functional Independence Measure motor scores were used as functional variables. RESULTS: Mean (SD) τAVO2diff was markedly shorter than τV˙O2 and τCO (26.1 [7.1] vs. 38.7 [10.2] and 46.6 [23.2 s], P<0.05), with no significant difference between τV˙O2 and τCO (P=0.444). The greater ratio of τCO to τV˙O2 was related to poorer motor function (rho=-0.484, P=0.026) and slower comfortable gait speed (r=-0.482, P=0.027). CONCLUSIONS: An increase in CO was slower than that in AVO2diff in patients with stroke. Therefore, V˙O2 kinetics in patients with stroke appears to be affected by a delayed increase in CO rather than AVO2diff. Furthermore, these patients with motor and gait impairments may have a poor matching of oxygen delivery and consumption during exercise onset.

Translatability of Scalp EEG Recordings of Duration-Deviant Mismatch Negativity Between Macaques and Humans: A Pilot Study.

Mismatch negativity (MMN) is a negative deflection of the auditory event-related potential (ERP) elicited by an abrupt change in a sound presented repeatedly. In patients with schizophrenia, MMN is consistently reduced, which makes it a promising biomarker. A non-human primate (NHP) model of MMN based on scalp electroencephalogram (EEG) recordings can provide a useful translational tool, given the high structural homology of the prefrontal and auditory cortices between NHPs, such as macaques, and humans. However, in previous MMN studies, the NHP models used did not allow for comparison with humans because of differences in task settings. Moreover, duration-deviant MMN (dMMN), whose reduction is larger than that in the frequency-deviant MMN (fMMN) in patients with schizophrenia, has never been demonstrated in NHP models. In this study, we determined whether dMMN can be observed in macaque scalp EEG recordings. EEGs were recorded from frontal electrodes (Fz) in two Japanese macaques. Consistent with clinical settings, auditory stimuli consisted of two pure tones, a standard and a deviant tone, in an oddball paradigm. The deviant and standard tones differed in duration (50 and 100 ms for the standard and deviant tones, respectively). A robust dMMN with a latency of around 200 ms, comparable to that in humans, was observed in both monkeys. A comparison with fMMN showed that the dMMN latency was the longer of the two. By bridging the gap between basic and clinical research, our results will contribute to the development of innovative therapeutic strategies for schizophrenia.

Cardiorespiratory factors related to the increase in oxygen consumption during exercise in individuals with stroke.

BACKGROUND: Understanding the cardiorespiratory factors related to the increase in oxygen consumption ([Formula: see text]) during exercise is essential for improving cardiorespiratory fitness in individuals with stroke. However, cardiorespiratory factors related to the increase in [Formula: see text] during exercise in these individuals have not been examined using multivariate analysis. This study aimed to identify cardiorespiratory factors related to the increase in [Formula: see text] during a graded exercise in terms of respiratory function, cardiac function, and the ability of skeletal muscles to extract oxygen. METHODS: Eighteen individuals with stroke (aged 60.1 ± 9.4 years, 67.1 ± 30.8 days poststroke) underwent a graded exercise test for the assessment of cardiorespiratory response to exercise. The increases in [Formula: see text] from rest to first threshold and that from rest to peak exercise were measured as a dependent variable. The increases in respiratory rate, tidal volume, minute ventilation, heart rate, stroke volume, cardiac output, and arterial-venous oxygen difference from rest to first threshold and those from rest to peak exercise were measured as the independent variables. RESULTS: From rest to first threshold, the increases in arterial-venous oxygen difference (ß = 0.711) and cardiac output (ß = 0.572) were significant independent variables for the increase in [Formula: see text] (adjusted R2 = 0.877 p < 0.001). Similarly, from rest to peak exercise, the increases in arterial-venous oxygen difference (ß = 0.665) and cardiac output (ß = 0.636) were significant factors related to the increase in [Formula: see text] (adjusted R2 = 0.923, p < 0.001). CONCLUSION: Our results suggest that the ability of skeletal muscle to extract oxygen is a major cardiorespiratory factor related to the increase in [Formula: see text] during exercise testing in individuals with stroke. For improved cardiorespiratory fitness in individuals with stroke, the amount of functional muscle mass during exercise may need to be increased.

Triphosphasumanene Trisulfide: High Out-of-Plane Anisotropy and Janus-Type π-Surfaces.

A triphosphasumanene trisulfide was designed and synthesized as an out-of-plane anisotropic π-conjugated molecule. Incorporating three anisotropic phosphine sulfide moieties into a sumanene skeleton induced a cumulative anisotropy with a large dipole moment (12.0 D), which is aligned in perpendicular direction with respect to the π-framework and more than twice as large as those of conventional out-of-plane anisotropic molecules. In the crystal, the molecules align to form columnar structures, in which electron-rich and electron-deficient sides of the π-framework face each other. The interactions between the electron-rich surfaces, which contain three sulfur atoms, and Au(111) were examined by X-ray photoelectron spectroscopy.

Context-Dependent Accumulation of Sensory Evidence in the Parietal Cortex Underlies Flexible Task Switching.

Switching behavior based on multiple rules is a fundamental ability of flexible behavior. Although interactions among the frontal, parietal, and sensory cortices are necessary for such flexibility, little is known about the neural computations concerning context-dependent information readouts. Here, we provide evidence that neurons in the lateral intraparietal area (LIP) accumulate relevant information preferentially depending on context. We trained monkeys to switch between direction and depth discrimination tasks and analyzed the buildup activity in the LIP depending on task context. In accordance with behavior, the rate of buildup to identical visual stimuli differed between tasks and buildup was prominent only for the stimulus dimension relevant to the task. These results indicate that LIP neurons accumulate relevant information depending on context to decide flexibly where to move the eye, suggesting that flexibility is, at least partly, implemented in the form of temporal integration gain control. SIGNIFICANCE STATEMENT: Flexible behavior depending on context is a hallmark of human cognition. During flexible behavior, the frontal and parietal cortices have complex representations that hinder efforts to conceptualize their underlying computations. We now provide evidence that neurons in the lateral intraparietal area accumulate relevant information preferentially depending on context. We suggest that behavioral flexibility is implemented in the form of temporal integration gain control in the parietal cortex.

A model of face selection in viewing video stories.

When typical adults watch TV programs, they show surprisingly stereo-typed gaze behaviours, as indicated by the almost simultaneous shifts of their gazes from one face to another. However, a standard saliency model based on low-level physical features alone failed to explain such typical gaze behaviours. To find rules that explain the typical gaze behaviours, we examined temporo-spatial gaze patterns in adults while they viewed video clips with human characters that were played with or without sound, and in the forward or reverse direction. We here show the following: 1) the "peak" face scanpath, which followed the face that attracted the largest number of views but ignored other objects in the scene, still retained the key features of actual scanpaths, 2) gaze behaviours remained unchanged whether the sound was provided or not, 3) the gaze behaviours were sensitive to time reversal, and 4) nearly 60% of the variance of gaze behaviours was explained by the face saliency that was defined as a function of its size, novelty, head movements, and mouth movements. These results suggest that humans share a face-oriented network that integrates several visual features of multiple faces, and directs our eyes to the most salient face at each moment.

A gait abnormality measure based on root mean square of trunk acceleration.

BACKGROUND: Root mean square (RMS) of trunk acceleration is seen frequently in gait analysis research. However, many studies have reported that the RMS value was related to walking speed. Therefore, the relationship between the RMS value and walking speed should be considered when the RMS value is used to assess gait abnormality. We hypothesized that the RMS values in three sensing axes exhibit common proportions for healthy people if they walk at their own preferred speed and that the RMS proportions in abnormal gait deviate from the common proportions. In this study, we proposed the RMS ratio (RMSR) as a gait abnormality measure and verified its ability to discriminate abnormal gait. METHODS: Forty-seven healthy male subjects (24-49 years) were recruited to examine the relationship between walking speed and the RMSR. To verify its ability to discriminate abnormal gait, twenty age-matched male hemiplegic patients (30-48 years) participated as typical subjects with gait abnormality. A tri-axial accelerometer was attached to their lower back, and they walked along a corridor at their own preferred speed. We defined the RMSR as the ratio between RMS in each direction and the RMS vector magnitude. RESULTS: In the healthy subjects, the RMS in all directions related to preferred walking speed. In contrast, RMSR in the mediolateral (ML) direction did not correlate with preferred walking speed (rs = -0.10, p = 0.54) and represented the similar value among the healthy subjects. Moreover, the RMSR in the ML direction for the hemiplegic patients was significantly higher than that for the healthy subjects (p < 0.01). CONCLUSIONS: These results suggest that the RMSR in the ML direction exhibits a common value when healthy subjects walk at their own preferred speed, even if their preferred walking speed were different. For subjects with gait abnormality, the RMSR in the ML direction deviates from the common value of healthy subjects. The RMSR in the ML direction may potentially be a quantitative measure of gait abnormality.

Maternal psychosocial factors determining the concentrations of transforming growth factor-beta in breast milk.

BACKGROUND: Cytokines in breast milk may play crucial roles in the beneficial effects of breastfeeding in protecting against allergic and infectious diseases in infants. In particular, breast milk-borne transforming growth factor-beta (TGF-ß) has an important potential role in developing the mucosal immune system in infants. However, little is known about what factors influence TGF-ß expression in human milk. We investigated whether the behavioral and psychosocial characteristics of mothers affect breast milk TGF-ß levels. METHODS: We conducted a survey of all 139 mothers who were lactating between February and October 2010 in Koshu City, Japan. Participants completed a questionnaire and provided breast milk at the health checkups for their 3-month-old child (N = 129, 93%). Breast milk was assayed for total TGF-ß2 levels by ELISA. We took an exploratory approach based on linear and ordered logistic regressions to model TGF-ß2 concentrations with their multiple potential determinants. RESULTS: Mothers with depression or poor self-rated health had higher TGF-ß2 concentrations than mothers without depression (odds ratio for a higher TGF-ß2 quartile: 3.11, 95% confidence intervals: 1.03-9.37) or those reporting better health (odds ratio: 2.34, 1.21-4.55). Smoking, drinking alcohol, probiotics supplementation, social support, and maternal history of allergic diseases were not associated with milk TGF-ß2 levels. Milk gathered between August and October or later in the afternoon (3-4 pm vs. 12-2 pm) contained less TGF-ß2. CONCLUSION: Depression, as the consequence of psychosocial stress, may be a strong determinant of TGF-ß levels in breast milk. Seasonal and daily fluctuations in milk TGF-ß2 concentrations warrant further study.