Multiple sclerosis and faecal microbiome transplantation: are you going to eat that?

Gut microbiome interaction goes beyond commensal function as vitamin production or support nutrients digestion. It also interplays with the host immune system and may be related to the development of immune-mediated diseases. Multiple sclerosis patients have dysbiosis compared to healthy individuals. But how this relates to disease development and severity is still uncertain. Dietary change including probiotic mixtures or ketogenic regimen has proven to change microbiome in multiple sclerosis (MS) subjects to one similar to healthy controls. However, proof of clinical benefits is lacking. We dissert on current knowledge about immune system and gut bacteria interactions. We discuss faecal microbial transplantation as a potential intervention to ameliorate gut dysbiosis in MS as well as the caveats of a clinical trial design.

Human bipedal instability in tree canopy environments is reduced by "light touch" fingertip support.

Whether tree canopy habitats played a sustained role in the ecology of ancestral bipedal hominins is unresolved. Some argue that arboreal bipedalism was prohibitively risky for hominins whose increasingly modern anatomy prevented them from gripping branches with their feet. Balancing on two legs is indeed challenging for humans under optimal conditions let alone in forest canopy, which is physically and visually highly dynamic. Here we quantify the impact of forest canopy characteristics on postural stability in humans. Viewing a movie of swaying branches while standing on a branch-like bouncy springboard destabilised the participants as much as wearing a blindfold. However "light touch", a sensorimotor strategy based on light fingertip support, significantly enhanced their balance and lowered their thigh muscle activity by up to 30%. This demonstrates how a light touch strategy could have been central to our ancestor's ability to avoid falls and reduce the mechanical and metabolic cost of arboreal feeding and movement. Our results may also indicate that some adaptations in the hand that facilitated continued access to forest canopy may have complemented, rather than opposed, adaptations that facilitated precise manipulation and tool use.

Biotransformation of trace organic chemicals during groundwater recharge: How useful are first-order rate constants?

This study developed relationships between the attenuation of emerging trace organic chemicals (TOrC) during managed aquifer recharge (MAR) as a function of retention time, system characteristics, and operating conditions using controlled laboratory-scale soil column experiments simulating MAR. The results revealed that MAR performance in terms of TOrC attenuation is primarily determined by key environmental parameters (i.e., redox, primary substrate). Soil columns with suboxic and anoxic conditions performed poorly (i.e., less than 30% attenuation of moderately degradable TOrC) in comparison to oxic conditions (on average between 70-100% attenuation for the same compounds) within a residence time of three days. Given this dependency on redox conditions, it was investigated if key parameter-dependent rate constants are more suitable for contaminant transport modeling to properly capture the dynamic TOrC attenuation under field-scale conditions. Laboratory-derived first-order removal kinetics were determined for 19 TOrC under three different redox conditions and rate constants were applied to MAR field data. Our findings suggest that simplified first-order rate constants will most likely not provide any meaningful results if the target compounds exhibit redox dependent biotransformation behavior or if the intention is to exactly capture the decline in concentration over time and distance at field-scale MAR. However, if the intention is to calculate the percent removal after an extended time period and subsurface travel distance, simplified first-order rate constants seem to be sufficient to provide a first estimate on TOrC attenuation during MAR.

Tuning the performance of a natural treatment process using metagenomics for improved trace organic chemical attenuation.

By utilizing high-throughput sequencing and metagenomics, this study revealed how the microbial community characteristics including composition, diversity, as well as functional genes in managed aquifer recharge (MAR) systems can be tuned to enhance removal of trace organic chemicals of emerging concern (CECs). Increasing the humic content of the primary substrate resulted in higher microbial diversity. Lower concentrations and a higher humic content of the primary substrate promoted the attenuation of biodegradable CECs in laboratory and field MAR systems. Metagenomic results indicated that the metabolic capabilities of xenobiotic biodegradation were significantly promoted for the microbiome under carbon-starving conditions.

Attentional focus of feedback for improving performance of reach-to-grasp after stroke: a randomised crossover study.

OBJECTIVE: To investigate whether feedback inducing an external focus (EF) of attention (about movement effects) was more effective for retraining reach-to-grasp after stroke compared with feedback inducing an internal focus (IF) of attention (about body movement). It was predicted that inducing an EF of attention would be more beneficial to motor performance. DESIGN: Crossover trial where participants were assigned at random to two feedback order groups: IF followed by EF or EF followed by IF. SETTING: Research laboratory. PARTICIPANTS: Forty-two people with upper limb impairment after stroke. INTERVENTION: Participants performed three reaching tasks: (A) reaching to grasp a jar; (B) placing a jar forwards on to a table; and (C) placing a jar on to a shelf. Ninety-six reaches were performed in total over one training session. MAIN OUTCOME MEASURES: Kinematic measures were collected using motion analysis. Primary outcome measures were movement duration, peak velocity of the wrist, size of peak aperture and peak elbow extension. RESULTS: Feedback inducing an EF of attention produced shorter movement durations {first feedback order group: IF mean 2.53 seconds [standard deviation (SD) 1.85]; EF mean 2.12 seconds (SD 1.63), mean difference 0.41 seconds; 95% confidence interval -0.68 to 1.5; P=0.008}, an increased percentage time to peak deceleration (P=0.01) when performing Task B, and an increased percentage time to peak velocity (P=0.039) when performing Task A compared with feedback inducing an IF of attention. However, an order effect was present whereby performance was improved if an EF of attention was preceded by an IF of attention. CONCLUSIONS: Feedback inducing an EF of attention may be of some benefit for improving motor performance of reaching in people with stroke in the short term; however, these results should be interpreted with caution. Further research using a randomised design is recommended to enable effects on motor learning to be assessed.

Grip force regulates hand impedance to optimize object stability in high impact loads.

Anticipatory grip force adjustments are a prime example of the predictive nature of motor control. An object held in precision grip is stabilized by fine adjustments of the grip force against changes in tangential load force arising from inertia during acceleration and deceleration. When an object is subject to sudden impact loads, prediction becomes critical as the time available for sensory feedback is very short. Here, we investigated the control of grip force when participants performed a targeted tapping task with a hand-held object. During the initial transport phase of the movement, load force varied smoothly with acceleration. In contrast, in the collision, load forces sharply increased to very large values. In the transport phase, grip force and load force were coupled in phase, as expected. However, in the collision, grip force did not parallel load force. Rather, it exhibited a stereotyped profile with maximum ∼65 ms after peak load at contact. By using catch trials and a virtual environment, we demonstrate that this peak of grip force is pre-programmed. This observation is validated across experimental manipulations involving different target stiffness and directions of movement. We suggest that the central nervous system optimizes stability in object manipulation-as in catching-by regulating mechanical parameters including stiffness and damping through grip force. This study provides novel insights about how the brain coordinates grip force in manipulation involving an object interacting with the environment.

Multisensory cues improve sensorimotor synchronisation.

Synchronising movements with events in the surrounding environment is an ubiquitous aspect of everyday behaviour. Often, information about a stream of events is available across sensory modalities. While it is clear that we synchronise more accurately to auditory cues than other modalities, little is known about how the brain combines multisensory signals to produce accurately timed actions. Here, we investigate multisensory integration for sensorimotor synchronisation. We extend the prevailing linear phase correction model for movement synchronisation, describing asynchrony variance in terms of sensory, motor and timekeeper components. Then we assess multisensory cue integration, deriving predictions based on the optimal combination of event time, defined across different sensory modalities. Participants tapped in time with metronomes presented via auditory, visual and tactile modalities, under either unimodal or bimodal presentation conditions. Temporal regularity was manipulated between modalities by applying jitter to one of the metronomes. Results matched the model predictions closely for all except high jitter level conditions in audio-visual and audio-tactile combinations, where a bias for auditory signals was observed. We suggest that, in the production of repetitive timed actions, cues are optimally integrated in terms of both sensory and temporal reliability of events. However, when temporal discrepancy between cues is high they are treated independently, with movements timed to the cue with the highest sensory reliability.

Being discrete helps keep to the beat.

Synchronizing our actions with external events is a task we perform without apparent effort. Its foundation relies on accurate temporal control that is widely accepted to take one of two different modes of implementation: explicit timing for discrete actions and implicit timing for smooth continuous movements. Here we assess synchronisation performance for different types of action and test the degree to which each action supports corrective updating following changes in the environment. Participants performed three different finger actions in time with an auditory pacing stimulus allowing us to assess synchronisation performance. Presenting a single perturbation to the otherwise regular metronome allowed us to examine corrections supported by movements varying in their mode of timing implementation. We find that discrete actions are less variable and support faster error correction. As such, discrete actions may be preferred when engaging in time-critical adaptive behaviour with people and objects in a dynamic environment.

Maintaining grip: anticipatory and reactive EEG responses to load perturbations.

Previous behavioral work has shown the existence of both anticipatory and reactive grip force responses to predictable load perturbations, but how the brain implements anticipatory control remains unclear. Here we recorded electroencephalographs while participants were subjected to predictable and unpredictable external load perturbations. Participants used precision grip to maintain the position of an object perturbed by load force pulses. The load perturbations were either distributed randomly over an interval 700- to 4,300-ms (unpredictable condition) or they were periodic with interval 2,000 ms (predictable condition). Preparation for the predictable load perturbation was manifested in slow preparatory brain potentials and in electromyographic and force signals recorded concurrently. Preparation modulated the long-latency reflex elicited by load perturbations with a higher amplitude reflex response for unpredictable compared with predictable perturbations. Importantly, this modulation was also reflected in the amplitude of sensorimotor cortex potentials just preceding the long-latency reflex. Together, these results support a transcortical pathway for the long-latency reflex and a central modulation of the reflex grip force response.

Knowing your nose better than your thumb: measures of over-grasp reveal that face-parts are special for grasping.

Typically, when a grasping response is made, the hand opens wider than the target object. We show that this "over-grasp" response is reduced when we reach to parts of our own face, relative to when we reach to other body parts or to neutral objects. This is not due to reaching to different parts of body space, as over-grasp responses are indifferent to whether or not other body parts or neutral objects are placed close to the face. It is also not due to differences in perceptual knowledge of the size of the target object. We conclude instead that the familiarity of face parts influences the grasping response directly. Subsequent experiments demonstrate that the movement representation determining any effect is not based on a torso-centred frame, and not abstracted from the specific hand used for grasping. We discuss the implications of the results for understanding and measuring motor representations for familiar actions.

Brain activity correlates differentially with increasing temporal complexity of rhythms during initialisation, synchronisation, and continuation phases of paced finger tapping.

Activity in parts of the human motor system has been shown to correlate with the complexity of performed motor sequences in terms of the number of limbs moved, number of movements, and number of trajectories. Here, we searched for activity correlating with temporal complexity, in terms of the number of different intervals produced in the sequence, using an overlearned tapping task. Our task was divided into three phases: movement selection and initiation (initiate), synchronisation of finger tapping with an external auditory cue (synchronise), and continued tapping in absence of the auditory pacer (continue). Comparisons between synchronisation and continuation showed a pattern in keeping with prior neuroimaging studies of paced finger tapping. Thus, activation of bilateral SMA and basal ganglia was greater in continuation tapping than in synchronisation tapping. Parametric analysis revealed activity correlating with temporal complexity during initiate in bilateral supplementary and pre-supplementary motor cortex (SMA and preSMA), rostral dorsal premotor cortex (PMC), basal ganglia, and dorsolateral prefrontal cortex (DLPFC), among other areas. During synchronise, correlated activity was observed in bilateral SMA, more caudal dorsal and ventral PMC, right DLPFC and right primary motor cortex. No correlated activity was observed during continue at P<0.01 (corrected, cluster level), though left angular gyrus was active at P<0.05. We suggest that the preSMA and rostral dorsal PMC activities during initiate may be associated with selection of timing parameters, while activation in centromedial prefrontal cortex during both initiate and synchronise may be associated with temporal error monitoring or correction. The absence of activity significantly correlated with temporal complexity during continue suggests that, once an overlearned timed movement sequence has been selected and initiated, there is no further adjustment of the timing control processes related to its continued production in absence of external cues.

Neurophysiological correlates of error correction in sensorimotor-synchronization.

In a sensorimotor synchronization task requiring subjects to tap in synchrony with an auditory stimulus, occasional perturbations (i.e., interval changes) in an otherwise isochronous sequence of auditory metronome stimuli are known to be compensated remarkably swift and with surprising precision, even when they are too small to be consciously perceived. To investigate the neural substrate and the informational basis of error correction in sensorimotor synchronization, we recorded movement-related, auditory-evoked, and error-related EEG potentials. Experiment 1 confirmed rapid adjustment to stimulus phase shifts, with faster correction of large (50 ms) compared to small (15 ms) shifts. In addition to being corrected faster, there was overcorrection of the 50 ms shifts, attributed to engagement of period correction mechanisms. For +50 ms shifts, a neural correlate of period correction was identified in the form of medial frontal cortex activation, preceded by an error-related brain potential (ERN). Auditory-evoked potential (AEP) amplitudes were sensitive to stimulus phase shifts of both large and small magnitude. Further experiments with a smaller magnitude 10 ms phase shift (Experiment 2) and passive auditory stimulation (Experiment 3) provided evidence that the modulation of AEP amplitudes is not due to metronome interval changes, but may represent auditory-somatosensory activation. Together, behavioral and neurophysiological data support the hypothesis that phase correction is a largely automatic process, not dependent on conscious perception of changes in timing. By contrast, perceivable phase shifts may invoke timekeeper adjustments accompanied by medial frontal cortex activity.

Efficiency of grip force adjustments for impulsive loading during imposed and actively produced collisions.

During object manipulation, both predictive feedforward and reactive feedback mechanisms are available to adjust grip force (GF) levels to compensate for the destabilizing effects of load force changes. During collisions, load force increases impulsively (< 20 ms). Thus, only predictive control of GF can be used to ensure grasp stabilization. A collision paradigm is here used to investigate the effects of practice and vision on the efficiency of the predictive control of GF. Subjects actively produced or received an imposed collision with a pendulum. Subjects were more efficient (used smaller GF for identical loads) when producing than when receiving the collisions. Effects of practice were evident in the active producing task only, with GF levels reducing over repetitions, suggesting that sensorimotor memory for the task was used to adjust GF more efficiently. With imposed collisions, GF levels did not reduce with repetition, which suggests that a direct relation between motor action and sensory feedback may be necessary to improve efficiency. Nevertheless, in this condition GF was lower with visual feedback, indicating potential for more efficient grip possibly associated with subjects degree of confidence. We discuss the implications of these results for accounts of the predictive and the reactive control of movement.

Proprioception-related evoked potentials: origin and sensitivity to movement parameters.

Reafferent electroencephalography (EEG) potentials evoked by active or passive movement are largely dependent on muscle spindle input, which projects to postrolandic sensory areas as well as the precentral motor cortex. The origin of these proprioception-related evoked potentials has previously been studied by using N20-P20 source locations of the median nerve somatosensory evoked potential as an landmark for postcentral area 3b. As this approach has yielded contradictory findings, likely due to spatial undersampling, we applied dipole source analysis on two independently collected sets of high-density EEG data, containing the proprioception-related N90 elicited by passive finger movement, and the N20-P20 elicited by median nerve stimulation. In addition, the influence of movement parameters on the N90 was explored by varying amplitude/duration and direction of passive movements. The results showed that the proprioceptive N90 component was not influenced by movement direction, but had a duration that covaried with the duration of the movement. Sources were localized in the precentral cortex, located on average 10 mm anterior to the N20-P20 sources. The latter result supports earlier claims that the motor cortex is involved in the generation of proprioception-related EEG potentials.

Effects of spatial and nonspatial cognitive activity on postural stability.

Is postural stability controlled automatically, or is it affected by concurrent cognitive activity? Are the effects influenced by the nature of the cognitive activity required, and do they increase in old age? To address these questions, 70 participants aged 20-79 years were asked to stand as still as possible on a force platform (postural control task) while performing (a) no cognitive task, (b) a spatial memory task, and (c) a nonspatial memory task. The memory tasks were also performed while seated as a comparison condition. Both spatial and nonspatial memory recall declined with increasing age but were unaffected by position (standing vs. seated). Postural stability declined with age; moreover, there was support for an earlier finding that age decline was greatest when performing the spatial memory task. Each recording period was split into two phases which, for the spatial and nonspatial memory tasks, corresponded to encoding and maintaining the stimuli. In comparison with no task, participants were more stable when encoding stimuli (particularly in the spatial task), but they were less stable when maintaining stimuli (particularly in the nonspatial task). The results suggest that postural stability can be affected by cognitive activity in complex ways, depending on the age of participants, the type of cognitive task (spatial vs. nonspatial), and the cognitive processing required (encoding vs. maintenance).

Estimating the minimum grip force required when grasping objects under impulsive loading conditions.

As an aid to studying the efficiency of grip force scaling in the context of collisions, we present a simple cost-effective approach to estimating the slip ratio--that is, the minimum grip-to-load-force ratio needed to prevent object slippage. The grip apparatus comprises a sturdy load cell to measure grip force and two linear potentiometers to provide detailed description of finger movements. The slip ratio was estimated by plotting the magnitude of finger movement against the grip-to-load-force ratio at the time of impact. The slip ratio was dependent on the direction of loading, which stresses the importance of estimating slip ratios in a context similar to that of the experiment in which the efficiency of subjects' behavior is to be assessed.

Brief bimanual force pulses: correlations between the hands in force and time.

Three experiments assessed coupling phenomena in the coordination of bimanual force pulses. Experiment 1 required symmetric force pulses (equal target forces and rise times for both hands) using the index finger of each hand. As the authors expected, on the basis of bimanual pointing movement results, this experiment revealed positive correlations between both the force rise times and the force amplitudes of the two hands. Experiments 2 and 3 included asymmetric conditions with different target force amplitudes (Experiment 2) or target rise times (Experiment 3). In Experiment 2 force amplitudes but not rise times were fully decoupled in the asymmetric condition. In the asymmetric condition of Experiment 3, however, neither rise times nor force amplitudes were fully decoupled. The results suggest a hierarchical control structure with temporal control dominating nontemporal control of bimanual force coordination.

Changing patterns of postural hip muscle activity during recovery from stroke.

OBJECTIVE: To describe the recovery of neurophysiological responses to perturbation of standing balance after stroke. METHODS: Surface electromyography (EMG) from hip abductors and adductors and ground reaction forces (GRF) were measured in response to 20 sideways pushes applied to the pelvis by a linear motor. Each subject's data from pushes in each direction were averaged and the presence of a muscle EMG response was assessed visually. SUBJECTS: Thirteen acute hemiplegic patients were tested as soon as they could stand after stroke (median six weeks) and serially during recovery. RESULTS: Four patterns of hip muscle activity were seen: (1) no response at all, (2) no response in hemiparetic muscles but compensation by contralateral muscles, (3) an appropriate, if delayed, response in the hemiparetic abductor but not adductor muscles, and (4) a relatively normal pattern in both hemiparetic muscles. Nine of 13 patients showed a change in pattern of hip muscle activity during recovery. All patients who initially resisted the sideways pushes solely with muscles of the unaffected leg later regained use of the hemiparetic hip abductors. CONCLUSIONS: The pattern of hip muscle activation changed towards normal during recovery from stroke in most patients. Use of compensatory strategies early after stroke in these subjects did not prevent return of normal patterns of muscle activation later.

Laboratory automation and optimization: the role of architecture.

The increasing automation of laboratory equipment has had far-reaching impacts on the organizational structure and spatial requirements of clinical laboratories. This report explores the changing role of the laboratory in the healthcare environment and shows the architectural impact of these changes, both inside and outside of the laboratory space.

Motor control: Mechanisms of motor equivalence in handwriting.

Handwriting is a classic example of how the details of movement can be scale and plane invariant: letter forms reflecting personal style are unchanged, whether one is writing on a piece of paper, on a blackboard or in the sand using the foot. Recent research points to a role for the parietal cortex in such motor equivalence.