Background: Wearing a harness during treadmill walking ensures the subject's safety and is common practice in biomedical engineering research. However, the extent to which such practice influences gait is unknown. This study investigated harness-related changes in gait patterns, as evaluated from lower extremity kinematics during treadmill walking.FindingsHealthy subjects (n=10) walked on a treadmill at their preferred speed for 3 minutes with and without wearing a harness (LiteGait, Mobility Research, Inc.). In the former condition, no weight support was provided to the subjects. Lower extremity kinematics was assessed in the sagittal plane from the mean (meanRoM), standard deviation (SDRoM) and coefficient of variation (CoVRoM) of the hip, knee, and ankle ranges of motion (RoM), as well as from the sample entropy (SampEn) and the largest Lyapunov exponent (LyE) of the joints' angles. Wearing the harness increased the meanRoM of the hip, the SDRoM and the CoVRoM of the knee, and the SampEn and the LyE of the ankle. In particular, the harness effect sizes for both the SampEn and the LyE of the ankle were large, likely reflecting a meaningful decline in the neuromuscular stabilizing control of this joint. Conclusions: Wearing a harness during treadmill walking marginally influences lower extremity kinematics, resulting in more or less subtle changes in certain kinematic variables. However, in cases where differences in gait patterns would be expressed through modifications in these variables, having subjects walk with a harness may mask or reinforce such differences.

Background: Sitting pivot transfer (SPT) is one of the most important, but at the same time strenuous at the upper extremity, functional task for spinal cord injured individuals. In order to better teach this task to those individuals and to improve performance, a better biomechanical understanding during the different SPT phases is a prerequisite. However, no consensus has yet been reached on how to depict the different phases of the SPT. The definition of the phases of the SPT, along with the events characterizing these phases, will facilitate the interpretation of biomechanical outcome measures related to the performance of SPTs as well as strengthen the evidence generated across studies. Methods: Thirty-five individuals with a spinal cord injury performed two SPTs between seats of similar height using their usual SPT technique. Kinematics and kinetics were recorded using an instrumented transfer assessment system. Based on kinetic and kinematic measurements, a relative threshold-based algorithm was developed to identify four distinct phases: pre-lift, upper arm loading, lift-pivot and post-lift phases. To determine the stability of the algorithm between the two SPTs, Student t-tests for dependent samples were performed on the absolute duration of each phase. Results: The mean total duration of the SPT was 2.00 +/- 0.01 s. The mean duration of the pre-lift, upper arm loading, lift-pivot and post-lift phases were 0.74 +/- 0.02 s, 0.28 +/- 0.01 s, 0.72 +/- 0.00 s, 0.27 +/- 0.01 s whereas their relative contributions represented approximately 35%, 15%, 35% and 15% of the overall SPT cycle, respectively. No significant differences were found between the trials (p=0.480-0.891). Conclusion: The relative threshold-based algorithm used to automatically detect the four distinct phases of the SPT, is rapid, accurate and repeatable. A quantitative and thorough description of the precise phases of the SPT is prerequisite to better interpret biomechanical findings and measure task performance. The algorithm could also become clinically useful to refine the assessment and training of SPTs.

Background: The motivation of patients during robot-assisted rehabilitation after neurological disorders that lead to impairments of motor functions is of great importance. Due to the increasing number of patients, increasing medical costs and limited therapeutic resources, clinicians in the future may want patients to practice their movements at home or with reduced supervision during their stay in the clinic. Since people only engage in an activity and are motivated to practice if the outcome matches the effort at which they perform, an augmented feedback application for rehabilitation should take the cognitive and physical deficits of patients into account and incorporate a mechanism that is capable of balancing i.e. adjusting the difficulty of an exercise in an augmented feedback application to the patient's capabilities. Methods: We propose a computational mechanism based on Fitts' Law that balances i.e. adjusts the difficulty of an exercise for upper-extremity rehabilitation. The proposed mechanism was implemented into an augmented feedback application consisting of three difficulty conditions (easy, balanced, hard). The task of the exercise was to reach random targets on the screen from a starting point within a specified time window. The available time was decreased with increasing condition difficulty. Ten subacute stroke patients were recruited to validate the mechanism through a study. Cognitive and motor functions of patients were assessed using the upper extremity section of the Fugl-Meyer Assessment, the modified Ashworth scale as well as the Addenbrookes cognitive examination-revised. Handedness of patients was obtained using the Edinburgh handedness inventory. Patients' performance during the execution of the exercises was measured twice, once for the paretic and once for the non-paretic arm. Results were compared using a two-way ANOVA. Post hoc analysis was performed using a Tukey HSD with a significance level of p < 0.05. Results: Results show that the mechanism was capable of balancing the difficulty of an exercise to the capabilities of the patients. Medians for both arms show a gradual decrease and significant difference of the number of successful trials with increasing condition difficulty (F2;60 = 44.623; p < 0.01; eta2 = 0.623) but no significant difference between paretic and non-paretic arm (F1;60 = 3.768; p = 0.057; eta2 = 0.065). Post hoc analysis revealed that, for both arms, the hard condition significantly differed from the easy condition (p < 0.01). In the non-paretic arm there was an additional significant difference between the balanced and the hard condition (p < 0.01). Reducing the time to reach the target, i.e., increasing the difficulty level, additionally revealed significant differences between conditions for movement speeds (F2;59 = 6.013; p < 0.01; eta2 = 0.185), without significant differences for hand-closing time (F2;59 = 2.620; p = 0.082; eta2 = 0.09), reaction time (F2;59 = 0.978; p = 0.383; eta2 = 0.036) and hand-path ratio (F2;59 = 0.054; p = 0.947; eta2 = 0.002). The evaluation of a questionnaire further supported the assumption that perceived performance declined with increased effort and increased exercise difficulty leads to frustration. Conclusions: Our results support that Fitts' Law indeed constitutes a powerful mechanism for task difficulty adaptation and can be incorporated into exercises for upper-extremity rehabilitation.

A brain-computer interface (BCI) is a communication system that can help users interact with the outside environment by translating brain signals into machine commands. The use of electroencephalographic (EEG) signals has become the most common approach for a BCI because of their usability and strong reliability. Many EEG-based BCI devices have been developed with traditional wet- or micro-electro-mechanical-system (MEMS)-type EEG sensors. However, those traditional sensors have uncomfortable disadvantage and require conductive gel and skin preparation on the part of the user. Therefore, acquiring the EEG signals in a comfortable and convenient manner is an important factor that should be incorporated into a novel BCI device. In the present study, a wearable, wireless and portable EEG-based BCI device with dry foam-based EEG sensors was developed and was demonstrated using a gaming control application. The dry EEG sensors operated without conductive gel; however, they were able to provide good conductivity and were able to acquire EEG signals effectively by adapting to irregular skin surfaces and by maintaining proper skin-sensor impedance on the forehead site. We have also demonstrated a real-time cognitive stage detection application of gaming control using the proposed portable device. The results of the present study indicate that using this portable EEG-based BCI device to conveniently and effectively control the outside world provides an approach for researching rehabilitation engineering.

Background: Both low-frequency repetitive transcranial magnetic stimulation (rTMS) and intensive occupational therapy (OT) have been recently reported to be clinically beneficial for post-stroke patients with upper limb hemiparesis. Based on these reports, we developed an inpatient combination protocol of these two modalities for the treatment of such patients. The aims of this pilot study were to confirm the safety and feasibility of the protocol in a large number of patients from different institutions, and identify predictors of the clinical response to the treatment. Methods: The study subjects were 204 post-stroke patients with upper limb hemiparesis (mean age at admission 58.5 ± 13.4 years, mean time after stroke 5.0 ± 4.5 years, ± SD) from five institutions in Japan. During 15-day hospitalization, each patient received 22 treatment sessions of 20-min low-frequency rTMS and 120-min intensive OT daily. Low-frequency rTMS of 1 Hz was applied to the contralesional hemisphere over the primary motor area. The intensive OT, consisting of 60-min one-to-one training and 60-min self-exercise, was provided after the application of low-frequency rTMS. Fugl-Meyer Assessment (FMA) and Wolf Motor Function Test (WMFT) were performed serially. The physiatrists and occupational therapists involved in this study received training prior to the study to standardize the therapeutic protocol. Results: All patients completed the protocol without any adverse effects. The FMA score increased and WMFT log performance time decreased significantly at discharge, relative to the respective values at admission (change in FMA score: median at admission, 47 points; median at discharge, 51 points; p < 0.001. change in WMFT log performance time: median at admission, 3.23; median at discharge, 2.51; p < 0.001). These changes were persistently seen up to 4 weeks after discharge in 79 patients. Linear regression analysis found no significant relationship between baseline parameters and indexes of improvement in motor function. Conclusions: The 15-day inpatient rTMS plus OT protocol is a safe, feasible, and clinically useful neurorehabilitative intervention for post-stroke patients with upper limb hemiparesis. The response to the treatment was not influenced by age or time after stroke onset. The efficacy of the intervention should be confirmed in a randomized controlled study including a control group.

Background: Compensatory trunk movements during gait, such as a Duchenne limp, are observed frequently in subjects with osteoarthritis of the hip, yet angular trunk movements are seldom included in clinical gait assessments. Hence, the objective of this study was to quantify compensatory trunk movements during gait in subjects with hip osteoarthritis, outside a gait laboratory, using a body-fixed-sensor based gait analysis. Frontal plane angular movements of the pelvis and thorax and spatiotemporal parameters of persons who showed a Duchenne limp during gait were compared to healthy subjects and persons without a Duchenne limp. Methods: A Body-fixed-sensor based gait analysis approach was used. Two body-fixed sensors were positioned at the dorsal side of the pelvis and on the upper thorax. Peak-to-peak frontal plane range of motion (ROM) and spatiotemporal parameters (walking speed, step length and cadence) of persons with a Duchenne limp during gait were compared to healthy subjects and persons without a Duchenne limp. Participants were instructed to walk at a self-selected low, preferred and high speed along a hospital corridor. Generalized estimating equations (GEE) analyses were used to assess group differences between persons with a Duchenne limp, without a Duchenne limp and healthy subjects. Results: Persons with a Duchenne limp showed a significantly larger thoracic ROM during walking compared to healthy subjects and to persons without a Duchenne limp. In both groups of persons with hip osteoarthritis, pelvic ROM was lower than in healthy subjects. This difference however only reached significance in persons without a Duchenne limp. The ratio of thoracic ROM relative to pelvic ROM revealed distinct differences in trunk movement patterns. Persons with hip osteoarthritis walked at a significantly lower speed compared to healthy subjects. No differences in step length and cadence were found between patients and healthy subjects, after correction for differences in walking speed. Conclusions: Distinctive patterns of frontal plane angular trunk movements during gait could be objectively quantified in healthy subjects and in persons with hip osteoarthritis using a body-fixed-sensor based gait analysis approach. Therefore, frontal plane angular trunk movements should be included in clinical gait assessments of persons with hip osteoarthritis.

Neurodegenerative disease: Preventing 'SIRTain' death by mutant huntingtin

Nature Reviews Neuroscience 13, 71 (2012). doi:10.1038/nrn3182

Author: Monica Hoyos Flight

Two independent studies link mutant huntingtin to inactivation of the deacetylase enzyme SIRT1 and highlight a neuroprotective role for SIRT1 in mouse models of Huntington's disease.

Neural development: Epigenetic regulation of asymmetry

Nature Reviews Neuroscience 13, 72 (2012). doi:10.1038/nrn3183

Author: Katherine Whalley

The brains of many species demonstrate structural and functional bilateral asymmetry, yet the underlying molecular mechanisms are mostly unknown. In the Caenorhabditis elegans nervous system, the lineages arising from the two daughter cells of a particular blastomere known as ABarap produce a different cell

Learning and memory: Becoming a habit: a role for NMDA receptors

Nature Reviews Neuroscience 13, 72 (2012). doi:10.1038/nrn3184

Author: Katherine Whalley

The actions of dopamine in the basal ganglia are important for the transformation of a repeated action into an automated habit; however, the precise mechanisms by which dopamine is modulated during habit learning are unclear. Here, the authors show that mice in which NMDAR1 is

Social neuroscience: Oxytocin boosts social awareness

Nature Reviews Neuroscience 13, 72 (2012). doi:10.1038/nrn3185

Author: Katherine Whalley

Sensitivity to the experiences of others contributes to many social behaviours including empathy and cooperation. Here, the authors show that oxytocin influences social behaviour in rhesus macaques in a context-dependent manner. When the monkeys had to choose whether to deliver a reward to another monkey

Neural development: Emergence of patterned activity in the motor system

Nature Reviews Neuroscience 13, 72 (2012). doi:10.1038/nrn3186

Author: Katherine Whalley

Spontaneous activity bursts contribute to network formation in many parts of the developing nervous system. Warp et al. used time-lapse imaging and optical manipulation of activity to investigate the emergence of spontaneous patterned activity in the developing zebrafish motor system. They found that the

Psychiatric disorders: Why two is better than one

Nature Reviews Neuroscience 13, 73 (2012). doi:10.1038/nrn3181

Author: Leonie Welberg

The antidepressant fluoxetine increases synaptic plasticity in the amygdala and thereby facilitates fear erasure through extinction.

Neural development: Clustering connections

Nature Reviews Neuroscience 13, 74 (2012). doi:10.1038/nrn3187

Author: Darran Yates

Repetitive spontaneous activity in developing neural networks causes spatiotemporal clustering of functional synapses on dendrites.

Brain evolution: MicroRNAs: big influence in brain evolution

Nature Reviews Neuroscience 13, 75 (2012). doi:10.1038/nrn3178

Author: Sian Lewis

It has been suggested that the rapid evolution of brain gene expression might partly account for the emergence of human cognition. Using microarrays and computational analysis, Somel et al. found that the rate of divergence of developmentally expressed genes in humans was 3–5 times

Ion channels: Optogenetics gets selective!

Nature Reviews Neuroscience 13, 75 (2012). doi:10.1038/nrn3179

Author: Sian Lewis

Optogenetic targeting of specific cell populations in rats has not been possible until now. A new study demonstrates a method for creating genetically restricted, recombinase-driven rat lines in which opsins can be expressed in specific populations of neurons. Witten et al. generated tyrosine hydroxylase–Cre

Neuronal circuits: Mapping the local field potential

Nature Reviews Neuroscience 13, 75 (2012). doi:10.1038/nrn3180

Author: Sian Lewis

The local field potential (LFP) is the low-frequency component of the extracellular voltage detected in the cortex, and changes in the LFP have been linked to many important processes, such as memory and motor function. Several recent reports have suggested that the LFP arises from

Activity-dependent neurotransmitter respecification

Nature Reviews Neuroscience 13, 94 (2012). doi:10.1038/nrn3154

Author: Nicholas C. Spitzer

For many years it has been assumed that the identity of the transmitters expressed by neurons is stable and unchanging. Recent work, however, shows that electrical activity can respecify neurotransmitter expression during development and in the mature nervous system, and an understanding is emerging of

Interneuron dysfunction in psychiatric disorders

Nature Reviews Neuroscience 13, 107 (2012). doi:10.1038/nrn3155

Author: Oscar Marín

Schizophrenia, autism and intellectual disabilities are best understood as spectrums of diseases that have broad sets of causes. However, it is becoming evident that these conditions also have overlapping phenotypes and genetics, which is suggestive of common deficits. In this context, the idea that the

Background: The evaluation of hand function impairment following a neurological disorder (stroke and cervical spinal cord injury) requires sensitive, reliable and clinically meaningful assessment tools. Clinical performance measures of hand function mainly focus on the accomplishment of activities of daily living (ADL), typically rather complex tasks assessed by a gross ordinal rating, while the motor performance (i.e. kinematics) is less detailed. The goal of this study was to develop a low-cost instrumented glove to capture details in grasping, feasible for the assessment of hand function in clinical practice and rehabilitation settings. Methods: Different sensor types were tested for output signal stability over time by measuring the signal drift of their step responses. A system that converted sensor output voltages into angles based on pre-measured curves was implemented. Furthermore, the voltage supply of each sensor signal conditioning circuit was increased to enhance the sensor resolution. The repeatability of finger bending trajectories, recorded during the performance of three ADL-based tasks, was established using the intraclass correlation coefficient (ICC). Moreover, the accuracy of the glove was evaluated by determining the agreement between angles measured with the embedded sensors and angles measured by traditional goniometry. In addition, the feasibility of the glove was tested in four patients with a pathological hand function caused by a cervical spinal cord injury (cSCI). Results: A sensor type that displayed a stable output signal over time was identified, and a high sensor resolution of 0.5 degrees was obtained. The evaluation of the glove's reliability yielded high ICC values (0.84 to 0.92) with an accuracy error of about +/- 5 degrees. Feasibility testing revealed that the glove was sensitive to distinguish different levels of hand function impairment in cSCI patients. Conclusions: The device satisfied the desired system requirements in terms of low cost, stable sensor signal over time, full finger-flexion range of motion tracking and capability to monitor all three joints of one finger. The developed rapid calibration system for easy use (high feasibility) and excellent psychometric properties (i.e. reliability and validity) qualify the device for the assessment of hand function in clinical practice and rehabilitation settings.

Background: To provide an alternative motor modality for control, navigation, and communication in individuals suffering from impairment or disability in hand functions, a Tongue Drive System (TDS) has been developed that allows for real time tracking of tongue motion in an unobtrusive, wireless, and wearable device that utilizes the magnetic field generated by a miniature disk shaped magnetic tracer attached to the tip of the tongue. The purpose of the study was to compare the influence of a concurrent motor or cognitive task on various aspects of simple movement control between hand and tongue using the TDS technology. Methods: Thirteen young able-bodied adults performed rapid and slow goal-directed movements of hand and tongue (with TDS) with and without a concurrent motor (hand or tongue) or cognitive (arithmetic and memory) task. Changes in reaction time, completion time, speed, correctness, accuracy, variability of displacement, and variability of time due to the addition of a concurrent task were compared between hand and tongue. Results: The influence of an additional concurrent task on motor performance was similar between the hand and tongue for slow movement in controlling their displacement. In rapid movement with a concurrent motor task, most aspects of motor performance were degraded in hand, while tongue speed during rapid continuous task was maintained. With a concurrent cognitive task, most aspects of motor performance were degraded in tongue, while hand accuracy during the rapid discrete task and hand speed during the rapid continuous task were maintained. Conclusion: Rapid goal-directed hand and tongue movements were more consistently susceptible to interference from concurrent motor and cognitive tasks, respectively, compared with the other movement.