Electrocortical activity correlated with locomotor adaptation during split-belt treadmill walking.

Locomotor adaptation is crucial for daily gait adjustments to changing environmental demands and obstacle avoidance. Mobile brain imaging with high-density electroencephalography (EEG) now permits quantification of electrocortical dynamics during human locomotion. To determine the brain areas involved in human locomotor adaptation, we recorded high-density EEG from healthy, young adults during split-belt treadmill walking. We incorporated a dual-electrode EEG system and neck electromyography to decrease motion and muscle artefacts. Voluntary movement preparation and execution have been linked to alpha (8-13 Hz) and beta band (13-30 Hz) desynchronizations in the sensorimotor and posterior parietal cortices, whereas theta band (4-7 Hz) modulations in the anterior cingulate have been correlated with movement error monitoring. We hypothesized that relative to normal walking, split-belt walking would elicit: (1) decreases in alpha and beta band power in sensorimotor and posterior parietal cortices, reflecting enhanced motor flexibility; and (2) increases in theta band power in anterior cingulate cortex, reflecting instability and balance errors that will diminish with practice. We found electrocortical activity in multiple regions that was associated with stages of gait adaptation. Data indicated that sensorimotor and posterior parietal cortices had decreased alpha and beta band spectral power during early adaptation to split-belt treadmill walking that gradually returned to pre-adaptation levels by the end of the adaptation period. Our findings emphasize that multiple brain areas are involved in adjusting gait under changing environmental demands during human walking. Future studies could use these findings on healthy, young participants to identify dysfunctional supraspinal mechanisms that may be impairing gait adaptation. KEY POINTS: Identifying the location and time course of electrical changes in the brain correlating with gait adaptation increases our understanding of brain function and provides targets for brain stimulation interventions. Using high-density EEG in combination with 3D biomechanics, we found changes in neural oscillations localized near the sensorimotor, posterior parietal and cingulate cortices during split-belt treadmill adaptation. These findings suggest that multiple cortical mechanisms may be associated with locomotor adaptation, and their temporal dynamics can be quantified using mobile EEG. Results from this study can serve as a reference model to examine brain dynamics in individuals with movement disorders that cause gait asymmetry and reduced gait adaptation.

A table tennis serve versus rally hit elicits differential hemispheric electrocortical power fluctuations.

Human visuomotor control requires coordinated interhemispheric interactions to exploit the brain's functional lateralization. In right-handed individuals, the left hemisphere (right arm) is better for dynamic control and the right hemisphere (left arm) is better for impedance control. Table tennis is a game that requires precise movements of the paddle, whole body coordination, and cognitive engagement, providing an ecologically valid way to study visuomotor integration. The sport has many different types of strokes (e.g., serve, return, and rally shots), which should provide unique cortical dynamics given differences in the sensorimotor demands. The goal of this study was to determine the hemispheric specialization of table tennis serving - a sequential, self-paced, bimanual maneuver. We used time-frequency analysis, event-related potentials, and functional connectivity measures of source-localized electrocortical clusters and compared serves with other types of shots, which varied in the types of movement required, attentional focus, and other task demands. We found greater alpha (8-12 Hz) and beta (13-30 Hz) power in the right sensorimotor cortex than in the left sensorimotor cortex, and we found a greater magnitude of spectral power fluctuations in the right sensorimotor cortex for serve hits than return or rally hits, in all right-handed participants. Surprisingly, we did not find a difference in interhemispheric functional connectivity between a table tennis serve and return or rally hits, even though a serve could arguably be a more complex maneuver. Studying real-world brain dynamics of table tennis provides insight into bilateral sensorimotor integration.NEW & NOTEWORTHY We found different spectral power fluctuations in the left and right sensorimotor cortices during table tennis serves, returns, and rallies. Our findings contribute to the basic science understanding of hemispheric specialization in a real-world context.

iCanClean Removes Motion, Muscle, Eye, and Line-Noise Artifacts from Phantom EEG.

The goal of this study was to test a novel approach (iCanClean) to remove non-brain sources from scalp EEG data recorded in mobile conditions. We created an electrically conductive phantom head with 10 brain sources, 10 contaminating sources, scalp, and hair. We tested the ability of iCanClean to remove artifacts while preserving brain activity under six conditions: Brain, Brain + Eyes, Brain + Neck Muscles, Brain + Facial Muscles, Brain + Walking Motion, and Brain + All Artifacts. We compared iCanClean to three other methods: Artifact Subspace Reconstruction (ASR), Auto-CCA, and Adaptive Filtering. Before and after cleaning, we calculated a Data Quality Score (0-100%), based on the average correlation between brain sources and EEG channels. iCanClean consistently outperformed the other three methods, regardless of the type or number of artifacts present. The most striking result was for the condition with all artifacts simultaneously present. Starting from a Data Quality Score of 15.7% (before cleaning), the Brain + All Artifacts condition improved to 55.9% after iCanClean. Meanwhile, it only improved to 27.6%, 27.2%, and 32.9% after ASR, Auto-CCA, and Adaptive Filtering. For context, the Brain condition scored 57.2% without cleaning (reasonable target). We conclude that iCanClean offers the ability to clear multiple artifact sources in real time and could facilitate human mobile brain-imaging studies with EEG.

iCanClean Improves Independent Component Analysis of Mobile Brain Imaging with EEG.

Motion artifacts hinder source-level analysis of mobile electroencephalography (EEG) data using independent component analysis (ICA). iCanClean is a novel cleaning algorithm that uses reference noise recordings to remove noisy EEG subspaces, but it has not been formally tested in a parameter sweep. The goal of this study was to test iCanClean's ability to improve the ICA decomposition of EEG data corrupted by walking motion artifacts. Our primary objective was to determine optimal settings and performance in a parameter sweep (varying the window length and r2 cleaning aggressiveness). High-density EEG was recorded with 120 + 120 (dual-layer) EEG electrodes in young adults, high-functioning older adults, and low-functioning older adults. EEG data were decomposed by ICA after basic preprocessing and iCanClean. Components well-localized as dipoles (residual variance < 15%) and with high brain probability (ICLabel > 50%) were marked as 'good'. We determined iCanClean's optimal window length and cleaning aggressiveness to be 4-s and r2 = 0.65 for our data. At these settings, iCanClean improved the average number of good components from 8.4 to 13.2 (+57%). Good performance could be maintained with reduced sets of noise channels (12.7, 12.2, and 12.0 good components for 64, 32, and 16 noise channels, respectively). Overall, iCanClean shows promise as an effective method to clean mobile EEG data.

Characterizing and Removing Artifacts Using Dual-Layer EEG during Table Tennis.

Researchers can improve the ecological validity of brain research by studying humans moving in real-world settings. Recent work shows that dual-layer EEG can improve the fidelity of electrocortical recordings during gait, but it is unclear whether these positive results extrapolate to non-locomotor paradigms. For our study, we recorded brain activity with dual-layer EEG while participants played table tennis, a whole-body, responsive sport that could help investigate visuomotor feedback, object interception, and performance monitoring. We characterized artifacts with time-frequency analyses and correlated scalp and reference noise data to determine how well different sensors captured artifacts. As expected, individual scalp channels correlated more with noise-matched channel time series than with head and body acceleration. We then compared artifact removal methods with and without the use of the dual-layer noise electrodes. Independent Component Analysis separated channels into components, and we counted the number of high-quality brain components based on the fit of a dipole model and using an automated labeling algorithm. We found that using noise electrodes for data processing provided cleaner brain components. These results advance technological approaches for recording high fidelity brain dynamics in human behaviors requiring whole body movement, which will be useful for brain science research.

Fatigue induces altered spatial myoelectric activation patterns in the medial gastrocnemius during locomotion.

This research investigates the effects of muscle fatigue on spatial myoelectric patterns in the lower limb during locomotion. Both spatial and frequency aspects of neuromuscular recruitment in the medial gastrocnemius change in response to fatigue, resulting in altered myoelectric patterns during walking and running. These data may help us better understand the adaptations that occur in lower limb muscles to avoid overuse injuries caused by fatigue.

Time to move: Brain dynamics underlying natural action and cognition.

Advances in Mobile Brain/Body Imaging (MoBI) technology allows for real-time measurements of human brain dynamics during every day, natural, real-life situations. This special issue Time to Move brings together a collection of experimental papers, targeted reviews and opinion articles that lay out the latest MoBI findings. A wide range of topics across different fields are covered including art, athletics, virtual reality, and mobility. What unites these diverse topics is the common goal to enhance and restore human abilities by reaching a better understanding on how cognition is implemented by the brain-body relationship. The breadth and novelty of paradigms and findings reported here positions MoBI as a new frontier in the field of human cognitive neuroscience.

Group-level cortical and muscular connectivity during perturbations to walking and standing balance.

Maintaining balance is a complex process requiring multisensory processing and coordinated muscle activation. Previous studies have indicated that the cortex is directly involved in balance control, but less information is known about cortical flow of signals for balance. We studied source-localized electrocortical effective connectivity dynamics of healthy young subjects (29 subjects: 14 male and 15 female) walking and standing with both visual and physical perturbations to their balance. The goal of this study was to quantify differences in group-level corticomuscular connectivity responses to sensorimotor perturbations during walking and standing. We hypothesized that perturbed visual input during balance would transiently decrease connectivity between occipital and parietal areas due to disruptive visual input during sensory processing. We also hypothesized that physical pull perturbations would increase cortical connections to central sensorimotor areas because of higher sensorimotor integration demands. Our findings show decreased occipito-parietal connectivity during visual rotations and widespread increases in connectivity during pull perturbations focused on central areas, as expected. We also found evidence for communication from cortex to muscles during perturbed balance. These results show that sensorimotor perturbations to balance alter cortical networks and can be quantified using effective connectivity estimation.

Energetics of Walking With a Robotic Knee Exoskeleton.

The authors tested 4 young healthy subjects walking with a powered knee exoskeleton to determine if it could reduce the metabolic cost of locomotion. Subjects walked with a backpack loaded and unloaded, on a treadmill with inclinations of 0° and 15°, and outdoors with varied natural terrain. Participants walked at a self-selected speed (average 1.0 m/s) for all conditions, except incline treadmill walking (average 0.5 m/s). The authors hypothesized that the knee exoskeleton would reduce the metabolic cost of walking uphill and with a load compared with walking without the exoskeleton. The knee exoskeleton reduced metabolic cost by 4.2% in the 15° incline with the backpack load. All other conditions had an increase in metabolic cost when using the knee exoskeleton compared with not using the exoskeleton. There was more variation in metabolic cost over the outdoor walking course with the knee exoskeleton than without it. Our findings indicate that powered assistance at the knee is more likely to decrease the metabolic cost of walking in uphill conditions and during loaded walking rather than in level conditions without a backpack load. Differences in positive mechanical work demand at the knee for varying conditions may explain the differences in metabolic benefit from the exoskeleton.

ExTzBox: A Glowing Cyclophane for Live-Cell Imaging.

The ideal fluorescent probe for live-cell imaging is bright and non-cytotoxic and can be delivered easily into the living cells in an efficient manner. The design of synthetic fluorophores having all three of these properties, however, has proved to be challenging. Here, we introduce a simple, yet effective, strategy based on well-established chemistry for designing a new class of fluorescent probes for live-cell imaging. A box-like hybrid cyclophane, namely ExTzBox·4X (6·4X, X = PF6-, Cl-), has been synthesized by connecting an extended viologen (ExBIPY) and a dipyridyl thiazolothiazole (TzBIPY) unit in an end-to-end fashion with two p-xylylene linkers. Photophysical studies show that 6·4Cl has a quantum yield ΦF = 1.00. Furthermore, unlike its ExBIPY2+ and TzBIPY2+ building units, 6·4Cl is non-cytotoxic to RAW 264.7 macrophages, even with a loading concentration as high as 100 µM, presumably on account of its rigid box-like structure which prevents its intercalation into DNA and may inhibit other interactions with it. After gaining an understanding of the toxicity profile of 6·4Cl, we employed it in live-cell imaging. Confocal microscopy has demonstrated that 64+ is taken up by the RAW 264.7 macrophages, allowing the cells to glow brightly with blue laser excitation, without any hint of photobleaching or disruption of normal cell behavior under the imaging conditions. By contrast, the acyclic reference compound Me2TzBIPY·2Cl (4·2Cl) shows very little fluorescence inside the cells, which is quenched completely under the same imaging conditions. In vitro cell investigations underscore the significance of using highly fluorescent box-like rigid cyclophanes for live-cell imaging.

Transient visual perturbations boost short-term balance learning in virtual reality by modulating electrocortical activity.

Immersive virtual reality can expose humans to novel training and sensory environments, but motor training with virtual reality has not been able to improve motor performance as much as motor training in real-world conditions. An advantage of immersive virtual reality that has not been fully leveraged is that it can introduce transient visual perturbations on top of the visual environment being displayed. The goal of this study was to determine whether transient visual perturbations introduced in immersive virtual reality modify electrocortical activity and behavioral outcomes in human subjects practicing a novel balancing task during walking. We studied three groups of healthy young adults (5 male and 5 female for each) while they learned a balance beam walking task for 30 min under different conditions. Two groups trained while wearing a virtual reality headset, and one of those groups also had half-second visual rotation perturbations lasting ~10% of the training time. The third group trained without virtual reality. We recorded high-density electroencephalography (EEG) and movement kinematics. We hypothesized that virtual reality training with perturbations would increase electrocortical activity and improve balance performance compared with virtual reality training without perturbations. Our results confirmed the hypothesis. Brief visual perturbations induced increased theta spectral power and decreased alpha spectral power in parietal and occipital regions and improved balance performance in posttesting. Our findings indicate that transient visual perturbations during immersive virtual reality training can boost short-term motor learning by inducing a cognitive change, minimizing the negative effects of virtual reality on motor training. NEW & NOTEWORTHY We found that transient visual perturbations in virtual reality during balance training can boost short-term motor learning by inducing a cognitive change, overcoming the negative effects of immersive virtual reality. As a result, subjects training in immersive virtual reality with visual perturbations have equivalent performance improvement as training in real-world conditions. Visual perturbations elicited cortical responses in occipital and parietal regions and may have improved the brain's ability to adapt to variations in sensory input.

Biomechanics and energetics of walking in powered ankle exoskeletons using myoelectric control versus mechanically intrinsic control.

BACKGROUND: Controllers for assistive robotic devices can be divided into two main categories: controllers using neural signals and controllers using mechanically intrinsic signals. Both approaches are prevalent in research devices, but a direct comparison between the two could provide insight into their relative advantages and disadvantages. We studied subjects walking with robotic ankle exoskeletons using two different control modes: dynamic gain proportional myoelectric control based on soleus muscle activity (neural signal), and timing-based mechanically intrinsic control based on gait events (mechanically intrinsic signal). We hypothesized that subjects would have different measures of metabolic work rate between the two controllers as we predicted subjects would use each controller in a unique manner due to one being dependent on muscle recruitment and the other not. METHODS: The two controllers had the same average actuation signal as we used the control signals from walking with the myoelectric controller to shape the mechanically intrinsic control signal. The difference being the myoelectric controller allowed step-to-step variation in the actuation signals controlled by the user's soleus muscle recruitment while the timing-based controller had the same actuation signal with each step regardless of muscle recruitment. RESULTS: We observed no statistically significant difference in metabolic work rate between the two controllers. Subjects walked with 11% less soleus activity during mid and late stance and significantly less peak soleus recruitment when using the timing-based controller than when using the myoelectric controller. While walking with the myoelectric controller, subjects walked with significantly higher average positive and negative total ankle power compared to walking with the timing-based controller. CONCLUSIONS: We interpret the reduced ankle power and muscle activity with the timing-based controller relative to the myoelectric controller to result from greater slacking effects. Subjects were able to be less engaged on a muscle level when using a controller driven by mechanically intrinsic signals than when using a controller driven by neural signals, but this had no affect on their metabolic work rate. These results suggest that the type of controller (neural vs. mechanical) is likely to affect how individuals use robotic exoskeletons for therapeutic rehabilitation or human performance augmentation.

Motor modules during adaptation to walking in a powered ankle exoskeleton.

BACKGROUND: Modules of muscle recruitment can be extracted from electromyography (EMG) during motions, such as walking, running, and swimming, to identify key features of muscle coordination. These features may provide insight into gait adaptation as a result of powered assistance. The aim of this study was to investigate the changes (module size, module timing and weighting patterns) of surface EMG data during assisted and unassisted walking in an powered, myoelectric, ankle-foot orthosis (ankle exoskeleton). METHODS: Eight healthy subjects wore bilateral ankle exoskeletons and walked at 1.2 m/s on a treadmill. In three training sessions, subjects walked for 40 min in two conditions: unpowered (10 min) and powered (30 min). During each session, we extracted modules of muscle recruitment via nonnegative matrix factorization (NNMF) from the surface EMG signals of ten muscles in the lower limb. We evaluated reconstruction quality for each muscle individually using R2 and normalized root mean squared error (NRMSE). We hypothesized that the number of modules needed to reconstruct muscle data would be the same between conditions and that there would be greater similarity in module timings than weightings. RESULTS: Across subjects, we found that six modules were sufficient to reconstruct the muscle data for both conditions, suggesting that the number of modules was preserved. The similarity of module timings and weightings between conditions was greater then random chance, indicating that muscle coordination was also preserved. Motor adaptation during walking in the exoskeleton was dominated by changes in the module timings rather than module weightings. The segment number and the session number were significant fixed effects in a linear mixed-effect model for the increase in R2 with time. CONCLUSIONS: Our results show that subjects walking in a exoskeleton preserved the number of modules and the coordination of muscles within the modules across conditions. Training (motor adaptation within the session and motor skill consolidation across sessions) led to improved consistency of the muscle patterns. Subjects adapted primarily by changing the timing of their muscle patterns rather than the weightings of muscles in the modules. The results of this study give new insight into strategies for muscle recruitment during adaptation to a powered ankle exoskeleton.

Effects of Cable Sway, Electrode Surface Area, and Electrode Mass on Electroencephalography Signal Quality during Motion.

More neuroscience researchers are using scalp electroencephalography (EEG) to measure electrocortical dynamics during human locomotion and other types of movement. Motion artifacts corrupt the EEG and mask underlying neural signals of interest. The cause of motion artifacts in EEG is often attributed to electrode motion relative to the skin, but few studies have examined EEG signals under head motion. In the current study, we tested how motion artifacts are affected by the overall mass and surface area of commercially available electrodes, as well as how cable sway contributes to motion artifacts. To provide a ground-truth signal, we used a gelatin head phantom with embedded antennas broadcasting electrical signals, and recorded EEG with a commercially available electrode system. A robotic platform moved the phantom head through sinusoidal displacements at different frequencies (0-2 Hz). Results showed that a larger electrode surface area can have a small but significant effect on improving EEG signal quality during motion and that cable sway is a major contributor to motion artifacts. These results have implications in the development of future hardware for mobile brain imaging with EEG.

Design and Validation of an Instrumented Uneven Terrain Treadmill.

Studying human and animal locomotion on an uneven terrain can be beneficial to basic science and applied studies for clinical and robotic applications. Traditional biomechanical analysis of human locomotion has often been limited to laboratory environments with flat, smooth runways and treadmills. The authors modified a regular exercise treadmill by attaching wooden blocks to the treadmill belt to yield an uneven locomotion surface. To ensure that these treadmill modifications facilitated biomechanical measurements, the authors compared ground reaction force data collected while a subject ran on the modified instrumented treadmill with a smooth surface with data collected using a conventional instrumented treadmill. Comparisons showed only minor differences. These results suggest that adding an uneven surface to a modified treadmill is a viable option for studying human or animal locomotion on an uneven terrain. Other types of surfaces (eg, compliant blocks) could be affixed in a similar manner for studies on other types of locomotion surfaces.

Restricted vision increases sensorimotor cortex involvement in human walking.

This study aimed to determine whether there is electrocortical evidence of augmented participation of sensory brain areas in walking modulation during walking with eyes closed. Healthy subjects (n = 10) walked on a treadmill at 1 m/s while alternating 5 min of walking with the eyes open or closed while we recorded ground reaction forces (GRFs) and high-density scalp electroencephalography (EEG). We applied independent component analysis to parse EEG signals into maximally independent component (IC) processes and then computed equivalent current dipoles for each IC. We clustered cortical source ICs and analyzed event-related spectral perturbations synchronized to gait events. Our results indicated that walking with eyes closed reduced the first peak of the vertical GRFs and induced shorter stride duration. Regarding the EEG, we found that walking with eyes closed induced significantly increased relative theta desynchronization in the frontal and premotor cortex during stance, as well as greater desynchronization from theta to beta bands during transition to single support for both left and right somatosensory cortex. These results suggest a phase-specific increased participation of brain areas dedicated to sensory processing and integration when vision is not available for locomotor guidance. Furthermore, the lack of vision demands higher neural processing related to motor planning and execution. Our findings provide evidence supporting the use of eyes-closed tasks in clinical practice, such as gait rehabilitation and improvements in balance control, as there is higher demand for additional sensory integration for achieving postural control.NEW & NOTEWORTHY We measured electrocortical dynamics in sighted individuals while walking with eyes open and eyes closed to induce the participation of other sensory systems in postural control. Our findings show that walking with visual restriction increases the participation of brain areas dedicated to sensory processing, motor planning, and execution. These results confirm the essential participation of supraspinal inputs to postural control in human locomotion, supporting the use of eyes-closed tasks in clinical practice.

Encapsulation of Ibuprofen in CD-MOF and Related Bioavailability Studies.

Although ibuprofen is one of the most widely used nonsteroidal anti-inflammatory drugs (NSAIDs), it exhibits poor solubility in aqueous and physiological environments as a free acid. In order to improve its oral bioavailability and rate of uptake, extensive research into the development of new formulations of ibuprofen has been undertaken, including the use of excipients as well as ibuprofen salts, such as ibuprofen lysinate and ibuprofen, sodium salt. The ultimate goals of these studies are to reduce the time required for maximum uptake of ibuprofen, as this period of time is directly proportional to the rate of onset of analgesic/anti-inflammatory effects, and to increase the half-life of the drug within the body; that is, the duration of action of the effects of the drug. Herein, we present a pharmaceutical cocrystal of ibuprofen and the biocompatible metal-organic framework called CD-MOF. This metal-organic framework (MOF) is based upon γ-cyclodextrin (γ-CD) tori that are coordinated to alkali metal cations (e.g., K+ ions) on both their primary and secondary faces in an alternating manner to form a porous framework built up from (γ-CD)6 cubes. We show that ibuprofen can be incorporated within CD-MOF-1 either by (i) a crystallization process using the potassium salt of ibuprofen as the alkali cation source for production of the MOF or by (ii) absorption and deprotonation of the free-acid, leading to an uptake of 23-26 wt % of ibuprofen within the CD-MOF. In vitro viability studies revealed that the CD-MOF is inherently not affecting the viability of the cells with no IC50 value determined up to a concentration of 100 µM. Bioavailability investigations were conducted on mice, and the ibuprofen/CD-MOF pharmaceutical cocrystal was compared to control samples of the potassium salt of ibuprofen in the presence and absence of γ-CD. From these animal studies, we observed that the ibuprofen/CD-MOF-1 cocrystal exhibits the same rapid uptake of ibuprofen as the ibuprofen potassium salt control sample with a peak plasma concentration observed within 20 min, and the cocrystal has the added benefit of a 100% longer half-life in blood plasma samples and is intrinsically less hygroscopic than the pure salt form.

A Boat-Shaped Tetracationic Macrocycle with a Semiconducting Organic Framework.

We report the synthesis of a tetracationic macrocycle which contains two N,N'-bis(methylene)naphthalenediimide units inserted in between the pyridinium rings of the bipyridinium units in cyclobis(paraquat-p-phenylene) (CBPQT4+ or "blue box") and describe the investigation of its potential use in materials for organic electronics. The incorporation of the two naphthalenediimide (NDI) units into the constitution of CBPQT4+ , not only changes the supramolecular properties of the tetracation in the solid state, but also has a profound influence on the electrochemical and electronic behavior of the resulting tetracationic macrocycle. In particular, the solid-state (super)structure, investigated by single-crystal X-ray diffraction, reveals the formation of a three-dimensional (3D) supramolecular framework with ca. 2.8 nm diameter one-dimensional (1D) hexagonal channels. Electrochemical studies on solid-state thin films of the macrocycle show that they exhibit semiconducting properties with a redox-conductivity of up to 7.6×10-4  S m-1 . Moreover, EPR and ENDOR spectroscopies show that charge is equally shared between the NDIs within the one-electron reduced state of the NDI-based macrocycle on the time scale of these techniques.

Cooperative Reactivity in an Extended-Viologen-Based Cyclophane.

A tetracationic pyridinium-based cyclophane with a box-like geometry, incorporating two juxtaposed alkyne functions, has been synthesized. The triple bonds are reactive through cycloadditions toward dienes and azides, promoted by the electron-withdrawing nature of the pyridinium rings, as well as by the strain inherent in the cyclophane. The cycloadditions proceeded in high yields, with the cyclophane reacting faster than its acyclic analogue. While the cyclophane contains two reactive triple bonds, there is no evidence for a stable monofunctional intermediate-only starting material and the difunctional product have been detected by (1)H NMR spectroscopy. Molecular modeling of the energy landscape reveals a lower barrier for the kinetically favored second cycloaddition compared with the first one. This situation results in tandem cascading reactions within rigid cyclophanes, where reactions at a first triple bond induce increased reactivity at a distal second alkyne.

Electrocortical activity distinguishes between uphill and level walking in humans.

The objective of this study was to determine if electrocortical activity is different between walking on an incline compared with level surface. Subjects walked on a treadmill at 0% and 15% grades for 30 min while we recorded electroencephalography (EEG). We used independent component (IC) analysis to parse EEG signals into maximally independent sources and then computed dipole estimations for each IC. We clustered cortical source ICs and analyzed event-related spectral perturbations synchronized to gait events. Theta power fluctuated across the gait cycle for both conditions, but was greater during incline walking in the anterior cingulate, sensorimotor and posterior parietal clusters. We found greater gamma power during level walking in the left sensorimotor and anterior cingulate clusters. We also found distinct alpha and beta fluctuations, depending on the phase of the gait cycle for the left and right sensorimotor cortices, indicating cortical lateralization for both walking conditions. We validated the results by isolating movement artifact. We found that the frequency activation patterns of the artifact were different than the actual EEG data, providing evidence that the differences between walking conditions were cortically driven rather than a residual artifact of the experiment. These findings suggest that the locomotor pattern adjustments necessary to walk on an incline compared with level surface may require supraspinal input, especially from the left sensorimotor cortex, anterior cingulate, and posterior parietal areas. These results are a promising step toward the use of EEG as a feed-forward control signal for ambulatory brain-computer interface technologies.