A global profile of germline gene expression in C. elegans.

We used DNA microarrays to profile gene expression patterns in the C. elegans germline and identified 1416 germline-enriched transcripts that define three groups. The sperm-enriched group contains an unusually large number of protein kinases and phosphatases. The oocyte-enriched group includes potentially new components of embryonic signaling pathways. The germline-intrinsic group, defined as genes expressed similarly in germlines making only sperm or only oocytes, contains a family of piwi-related genes that may be important for stem cell proliferation. Finally, examination of the chromosomal location of germline transcripts revealed that sperm-enriched and germline-intrinsic genes are nearly absent from the X chromosome, but oocyte-enriched genes are not.

Effectiveness of supplemental grasp-force feedback in the presence of vision.

Previous studies have shown that supplemental grasp-force feedback can improve control for users of a hand prosthesis or neuroprosthesis under conditions where vision provides little force information. Visual cues of force are widely available in everyday use, however, and may obviate the utility of supplemental force information. The purpose of the present study was to use a video-based hand neuroprosthesis simulator to determine whether grasp-force feedback can improve control in the presence of realistic visual information. Seven able-bodied subjects used the simulator to complete a simple grasp-and-hold task while controlling and viewing pre-recorded, digitised video clips of a neuroprosthesis user's hand squeezing a compliant object. The task was performed with and without supplemental force feedback presented via electrocutaneous stimulation. Subjects had to achieve and maintain the (simulated) grasp force within a target window of variable size (+/- 10-40% of full scale). Force feedback improved the success rate significantly for all target window sizes (8-16%, on average), and improved the success rate at all window sizes for six of the seven subjects. Overall, the improvement was equivalent functionally to a 35% increase in the window size. Feedback also allowed subjects to identify the direction of grasp errors more accurately, on average by 10-15%. In some cases, feedback improved the failure identification rate even if success rates were unchanged. It is thus concluded that supplemental grasp-force feedback can improve grasp control even with access to rich visual information from the hand and object.

A high voltage, constant current stimulator for electrocutaneous stimulation through small electrodes.

A high-voltage stimulator has been designed to allow transcutaneous stimulation of tactile fibers of the fingertip. The stimulator's output stage was based upon an improved Howland current pump topology, modified to allow high load impedances and small currents. The compliance voltage of approximately 800 V is achieved using commercially available high-voltage operational amplifiers. The output current accuracy is better than +/- 5% over the range of 1 to 25 mA for 30 microseconds or longer pulses. The rise time for square pulses is less than 1 microsecond. High-voltage, common-mode, latch-up power supply problems and solutions are discussed. The stimulator's input stage is optically coupled to the controlling computer and complies with applicable safety standards for use in a hospital environment. The design presented here is for monophasic stimulation only, but could be modified for biphasic stimulation.

Satisfaction with and usage of a hand neuroprosthesis.

OBJECTIVE: To measure the satisfaction with, clinical impact of, and use of an implantable hand neuroprosthesis. SETTING: Eight different medical centers. PARTICIPANTS: Thirty-four individuals with spinal cord injuries at the C5 or C6 motor level. INTERVENTIONS: Participants were implemented with a hand neuroprosthesis that provides grasp and release. The neuroprosthesis includes a surgically implanted stimulator, implanted electrodes sutured to the hand and forearm muscles, and an externally mounted controller. MAIN OUTCOME MEASURE: A survey was mailed to study participants, who were asked to respond to statements such as "If I had it to do over, I would have the hand system implanted again," using a 5-level Likert scale ("strongly agree" to "strongly disagree"). RESULTS: Eighty-seven percent of participants were very satisfied with the neuroprosthesis, 88% reported a positive impact on their life, 87% reported improvements in activities of daily living, and 81% reported improved independence. Participants reported using the neuroprosthesis a median of 5.5 days per week; 15 participants used the neuroprosthesis 7 days per week, and 5 participants reported not using the device. CONCLUSIONS: The neuroprosthesis was used by most participants. The neuroprosthesis performed satisfactorily, increased users' ability to perform activities of daily living and independence, and improved their quality of life.

Isolation of zebrafish gdf7 and comparative genetic mapping of genes belonging to the growth/differentiation factor 5, 6, 7 subgroup of the TGF-beta superfamily.

The Growth/differentiation factor (Gdf) 5, 6, 7 genes form a closely related subgroup belonging to the TGF-beta superfamily. In zebrafish, there are three genes that belong to the Gdf5, 6, 7 subgroup that have been named radar, dynamo, and contact. The genes radar and dynamo both encode proteins most similar to mouse GDF6. The orthologous identity of these genes on the basis of amino acid similarities has not been clear. We have identified gdf7, a fourth zebrafish gene belonging to the Gdf5, 6, 7 subgroup. To assign correct orthologies and to investigate the evolutionary relationships of the human, mouse, and zebrafish Gdf5, 6, 7 subgroup, we have compared genetic map positions of the zebrafish and mammalian genes. We have mapped zebrafish gdf7 to linkage group (LG) 17, contact to LG9, GDF6 to human chromosome (Hsa) 8 and GDF7 to Hsa2p. The radar and dynamo genes have been localized previously to LG16 and LG19, respectively. A comparison of syntenies shared among human, mouse, and zebrafish genomes indicates that gdf7 is the ortholog of mammalian GDF7/Gdf7. LG16 shares syntenic relationships with mouse chromosome (Mmu) 4, including Gdf6. Portions of LG16 and LG19 appear to be duplicate chromosomes, thus suggesting that radar and dynamo are both orthologs of Gdf6. Finally, the mapping data is consistent with contact being the zebrafish ortholog of mammalian GDF5/Gdf5.

Grasp stiffness as a function of grasp force and finger span.

The purpose of this study was to determine whether direct measurements of grasp stiffness agreed with stiffness inferred from the slopes of isovolitional force-space characteristics derived from previous grasp-effort matching data. Grasp stiffness for three-finger pinch was measured as a function of initial force and finger span using step displacements applied in a do-not-intervene paradigm. Subjects pinched a free-floating, motorized manipulandum in each hand and squeezed both with equal effort; one of the hands was perturbed at random. Stiffness was calculated from the initial and final steady-state values of force and span. The effects of step amplitude, rise-time, and initial load stiffness were investigated; grasp stiffness decreased significantly for larger steps, increased slightly for longer rise-times, and was unaffected by load stiffness. Grasp stiffness then was measured as a function of initial force and span using a single set of step parameters. Stiffness increased significantly in proportion to force but was changed only slightly by span. It was concluded that the perturbation and effort-matching measures of stiffness are not equivalent and represent different components of motor behavior.

Differential effects of load stiffness on matching pinch force, finger span, and effort.

Disparities in load stiffness were used to differentiate and characterize pinch-force, finger-span, and pinch-effort matching in two experiments. All subjects squeezed a spring-loaded manipulandum in each hand using three-finger pinch. Subjects in the first experiment were instructed explicitly to match one of the three continua. Subjects matching force or span were told to attend carefully to sensations from the hand or arm and to ignore differences in the effort required to make the sensations equal. They had to achieve and hold a particular target force with the reference hand and then match force or span with the opposite hand, usually against a spring with a different stiffness. These subjects were given as much time as necessary to make their matches and were told which hand was serving as the reference in each trial. Effort-matching subjects were told to ignore peripheral sensations and to match effort or motor commands. These subjects were not told which hand was the reference and were given only 1 s to make a match, so they made matches by rapidly squeezing both manipulanda simultaneously and, presumably, with the same voluntary motor command. The matching behaviors of the three groups were clearly distinguishable and were consistent with instructions. Results were similar whether different subjects were assigned different instructions or the same subjects performed all three match types. In a second experiment, naïve subjects were given purposely ambiguous instructions without reference to a specific continuum and had no time or accuracy constraints. Subjects produced the same three sensorimotor behaviors obtained with explicit instructions, showing that the different behaviors were not artifacts of strict protocols. Taken together, the results show that force, span, and effort are distinct sensorimotor continua that can be judged reliably.

Contours of equal perceived amplitude and equal perceived frequency for electrocutaneous stimuli.

Previous measurements of equal-sensation contours for electrocutaneous stimuli consisting of repeated bursts of biphasic pulses have shown that stimulus frequency has little effect on perceived amplitude, and that stimulus amplitude has no effect on perceived frequency. These earlier contours, however, were measured over a very restricted range of amplitude and frequency or for a single perceived amplitude or perceived frequency. Contours of equal perceived amplitude and equal perceived frequency were measured in the present study for stimuli covering most of the useable range of amplitudes and frequencies: 3-12 dB SL and 4-64 Hz. Eight naïve subjects generated contours of equal perceived amplitude at four reference amplitudes via Békésy tracking, and 8 additional subjects generated contours of equal perceived frequency at three reference frequencies. The contours of equal perceived amplitude declined slightly but significantly with increases in stimulus frequency, consistent with previous results. The shape of the contours was also slightly dependent on the amplitude of the reference stimulus. Contours of equal perceived frequency were unaffected by stimulus amplitude on the average, but the contour shape did vary modestly, though erratically, with reference frequency.

Halving and doubling isometric force: evidence for a decelerating psychophysical function consistent with an equilibrium-point model of motor control.

Several previous investigations have measured accelerating psychophysical functions for perceived force with exponents of about 1.7. Two halving and doubling experiments presented here imply a psychophysical function for perceived force with an exponent between 0.6 and 0.8. That is, more than a doubling of force was needed to double the sensation, and similarly for halving. In the first experiment, subjects squeezed rigid instrumented cylinders between the thumb and first two fingers of each hand. They generated and released a reference force with one hand, and then squeezed the opposite hand to produce a sensation magnitude equal to, twice that, or half that of the reference. An analysis using a model that accounted for compression bias yielded average psychophysical functions with exponents of 0.58 and 0.59 (nondominant and dominant hands, respectively). The second experiment was an attempt to replicate earlier results and to reconcile them with the first experiment by using a paradigm duplicated from a previous study. Subjects in the second experiment made unilateral halving and doubling judgments of handgrip while squeezing a hand dynamometer. Again, the halving and doubling judgments yielded decelerating functions with exponents of 0.75 and 0.80 (nondominant and dominant hands, respectively). Even though the results of the first two experiments contradict earlier investigations, they can be explained by an equilibrium model of motor control assuming that subjects halve and double the central motor command rather than the sensation of force. The force is simply the result of the mechanical equilibrium established between the load and the compliant effector (the hand). The predicted relationship between the motor command judgments, the compliance of the hand, and the resultant forces was confirmed in a third experiment in which the mechanical compliance of the three-finger pinch was measured by using a pneumatic manipulandum to apply force perturbations in a "do-not-intervene" paradigm. The measured compliance characteristic was accelerating, just as predicted by the model, in order to produce a decelerating psychophysical function for "perceived force." In this experiment, then, judgments of perceived force appear to be judgments of the central motor command.

Perspectives on the role of afferent signals in control of motor neuroprostheses.

K.O. Johnson reviews the architecture and low level neural mechanisms by which the external environment is transduced and encoded into the neural system, summarizing work that correlates neurophysiological and psychophysical testing with isolation of sensory components. The slowly adapting Type I afferent system is responsible for form and texture perception; the rapidly adapting afferent system is responsible for motion perception; and the Pacinian corpuscle system is responsible for vibratory sensation. R.R. Riso reviews the current level of understanding of the major factors to be considered in the design of a functional neuromuscular stimulation (FNS) grasp controller that uses cutaneous sensory feedback to detect slip. The elegant natural control scheme that matches the ratio of grip and lift forces to frictional conditions provides a model for implementing a slip-based control algorithm. D. Popovic discusses the possible use of recordings from more proximal peripheral nerves to determine needed information for synthesis of locomotion. The discussion is illustrated with an animal model where rule-based closed-loop control is used for the ankle joint during treadmill locomotion. Neural signals from the tibial and superficial peroneal nerves were employed to substitute for missing afferent input from cutaneous and proprioceptive sensors. The feasibility of more invasive intraneural electrodes for distinguishing sensory from motor information in mixed nerves is considered. M. Koris raises surgical and functional issues relevant to developing clinical FNS systems. C. Van Doren suggests alternative neurophysiological and engineering approaches.

The effects of afferent stimulation on congenital nystagmus foveation periods.

Visual acuity in congenital nystagmus (CN) patients is related primarily to the duration of "foveation periods", during which the image of the target is relatively stationary in the foveal area. Thirteen individuals with CN were studied to test the hypothesis that somatosensory stimulation (vibration or electrical) of either the forehead or the neck damps CN and improves visual acuity. We identified characteristics of the nystagmus waveform that were likely to be important in determining visual acuity and combined these measures into an "acuity function" (NAFP) that correlated well with visual acuity (r2 = 0.91). Statistically significant changes in NAFP were used to assess the effects of afferent stimulation; positive effects were found in nine subjects. Vibratory stimulation (especially on the neck) was found to be more effective than electrical stimulation. CN amplitude reduction alone was neither necessary nor sufficient to improve acuity. Foveation duration was the single most important factor determining acuity. Based on our findings, afferent stimulation should be considered as an alternative or additional treatment to improve visual acuity in CN patients.

Cross-modality matches of finger span and line length.

Perceived finger span--the perceived spatial separation between the tip of the thumb and the tip of the index finger--was measured by using cross-modal matching to line length. In the first experiment, subjects adjusted finger span to match the length of line segments presented on a video monitor, and conversely, with both hands. Subjects also made estimates of finger span in physical units ("dead reckoning"). Finger spans were measured by using infrared LEDs mounted on the tip of the thumb and the finger tip, so the hand made no contact with any object during the experiment. Unlike in previous studies, the results suggest that perceived finger span is proportional to line length and slightly shorter than the actual span, provided that corrections are made for regression bias. The effect of finger contact was assessed in a second experiment by matching line length both to free span and to spans constrained by the pinching of blocks in the same session. The matching function when subjects were pinching blocks was accelerating, consistent with previous reports. In contrast, matched line length was a decelerating function of free span. The exponent of the free span matching function in the second experiment was slightly smaller than in the first experiment, probably due to uncorrected matching biases in the second experiment.

Pinch force matching errors predicted by an equilibrium-point model.

Varying the size or stiffness of an external load often results in systematic grasp force or finger span matching errors, typically judged via contralateral matching. In the present study, subjects squeezed compliant or rigid manipulanda in each hand using three-finger pinch in order to generate, and simultaneously match, a reference force indicated by a visual cue. Subjects were not informed which hand was the reference and were given only 1 s to make a match. Under these conditions, subjects appeared to match central commands rather than perceived force. Forces were always exaggerated when squeezing an isometric load to match a compliant load and were too small when matching a compliant load to an isometric load. The matching errors were largest for the most compliant spring and increased with the reference force. When the loads were symmetric (e.g., both compliant), errors were small, but subjects persistently squeezed slightly harder with the left (non-dominant) hand. Apart from the left-hand bias, the matching results agree quantitatively and in detail with the predictions of an equilibrium point model (the lambda model), in which central commands shift the rest length of spring-like muscle. The matching data are fit best assuming that the muscle's compliance characteristic is an accelerating function, in agreement with previous direct measurements of pinch stiffness.

Development of a quantitative hand grasp and release test for patients with tetraplegia using a hand neuroprosthesis.

We developed a quantitative grasp and release test for assessing a hand neuroprosthesis in C5 and C6 level tetraplegic patients. The objectives were (1) to determine if a patient's hand performance with the neuroprosthesis exceeded a defined, clinically acceptable baseline, (2) to compare performance with and without the neuroprosthesis, (3) to measure the consistency of performance over time, and (4) to compare performance among patients. In the test, patients grasped, moved, and released one of six different objects as many times as possible in five 30-second trials for each object, with and without the neuroprosthesis. Unlike earlier tests, the objects and the task were chosen to span a range of difficulties appropriate for C5 and C6 tetraplegic patients using a hand neuroprosthesis. Data from five patients showed that performance with the neuroprosthesis was above the baseline; performance improved with the neuroprosthesis, although it was not generally consistent across sessions; and the neuroprosthesis helped C5 patients manipulate most objects and helped C6 patients primarily with more difficult objects.

Individual differences in perceived pinch force and bite force.

Six subjects made cross-modal matches of pinch force and bite force to an electrocutaneous stimulus. The electrocutaneous stimulus consisted of bursts of pulses, and the intensity of the stimulus was varied by changing the number of pulses per burst. All of the individual matching functions were fit well by power functions. The scaling constants and exponents of the power functions covaried systematically with the maximum pinch force for 5 of the 6 subjects. The relationship was consistent with the hypothesis that subjects perceive their physical maxima equally, in agreement with Borg's theory of relative perceived exertion. For both pinch force and bite force functions, the scale factors could be described by a single linear function of the exponents, suggesting that all of the matching functions converged at a single point with extreme values.

The effect of electrical stimulation on quadriceps femoris muscle torque in children with spina bifida.

The effects of neuromuscular electrical stimulation (NMES) on the torque production of the quadriceps femoris muscles were examined in five children with spina bifida. Two male subjects, aged 5 and 12 years, and three female subjects, aged 5, 12, and 21 years, participated in the study. Surface stimulation was applied to the quadriceps femoris muscles of one lower extremity for 30 minutes each day over an 8-week period. At 0, 4, and 8 weeks, maximum isometric voluntary knee extension torques were measured for both control and stimulated lower extremities with a dynamometer at 0, 15, 30, 45, and 60 degrees of knee flexion. The three oldest subjects had torque measurements of acceptable reliability (intraclass correlation coefficient greater than .72). Two of these three subjects also had significant increases in the torque produced by the stimulated limb relative to the torque produced by the control limb. The data were unreliable from the two youngest subjects. Completion times for functional tasks (walking and step ascension/descension) were also recorded before and after the 8 weeks of stimulation. The completion times were lower following stimulation for four subjects.

Functional evaluation of quadriplegic patients using a hand neuroprosthesis.

The objective of this retrospective study was to compare the abilities of quadriplegic patients to complete activities of daily living with and without the use of a portable hand neuroprosthesis. The neuroprosthesis provided synthetic hand grasp through functional neuromuscular stimulation of paralyzed forearm and hand muscles. Data were obtained from telephone interviews, patient records, and videotapes. Twenty-two quadriplegic patients were included in the study; 15 were functional at a C5 spinal cord injury level and seven at a C6 level. The median success rate (ie, the percentage of patients who could complete each activity) across the ten activities was 89% with the hand neuroprosthesis but was only 49% without the hand neuroprosthesis. All patients could perform more tasks when the neuroprosthesis was used, although the relative improvement of C5 patients was larger than that of C6 patients.

The effects of a surround on vibrotactile thresholds: evidence for spatial and temporal independence in the non-Pacinian I (NPI) channel.

Detection thresholds were measured for sinusoidal vibrations applied to the thenar eminence and volar forearm. Stimuli were applied via a 0.72-cm2 circular contactor, with and without a rigid surround. At low frequencies, below about 40 Hz, the thresholds were higher without the surround than with the surround. However, in contrast to earlier reports, the shape of the threshold function was the same with and without the surround, suggesting that the temporal and spatial tuning characteristics of the non-Pacinian I (NPI) channel are independent.

Vibrotactile temporal gap detection as a function of age.

The ability of subjects to detect temporal gaps between bursts of sinusoids or bursts of bandlimited noise was measured to evaluate the phenomenon of tactile "sensory persistence" in older persons. Vibratory stimuli were delivered to the right thenar eminence of 27 subjects ranging in age from 8-75 years. The subjects' task was to detect the presence of a silent interval or "gap" between flanking 350-ms vibrotactile stimuli. The gap-detection threshold, expressed as the amplitude of vibration relative to the absolute detection threshold, decreased as the gap duration increased and was higher for gaps in noise than for gaps in sinusoids. The threshold for detecting short gaps increased with age for noise stimuli, but not for sinusoidal stimuli. Furthermore, the gap-detection threshold recovered more rapidly in older subjects for noise stimuli, but less rapidly in older subjects for sinusoidal stimuli. Because of these differences, it appears that the effects of age on gap detection cannot be due to a simple increase in sensory persistence, but may be due to multiple processes.

A model of spatiotemporal tactile sensitivity linking psychophysics to tissue mechanics.

Sensitivities were measured for tangible spatiotemporal sinusoids applied to the index fingertip. The sinusoids had temporal frequencies of 8 and 128 Hz, in order to selectively activate the non-Pacinian I (NP I) and Pacinian (P) cutaneous mechanoreceptor systems, respectively, and had spatial frequencies from 0.00-1.03 cycles/mm. The sensitivity of the NP I system increased as the spatial frequency increased, whereas the sensitivity of the P system generally decreased as the spatial frequency increased. A mechanical model of the fingertip was used to calculate the normal and shear strains in the tissue, and a psychophysical linking hypothesis was introduced to predict tactile sensitivities based on the calculated strains. Specifically, the fingertip was modeled as a slab of a linear, isotropic, homogeneous, viscoelastic material. The boundary conditions were imposed by the spatiotemporal sinusoid at the top of the slab and the rigidly attached bone at the bottom of the slab. It was then assumed that the detection threshold was equal to the stimulus amplitude, which produced a constant, criterion strain at the location of the receptor. For both the P and NP I responses, the agreement between the predicted and measured sensitivities was best for calculations based on the normal strain, and for spatial frequencies below 0.5 cycles/mm. At higher spatial frequencies, the measured sensitivities were higher than predicted. The model also predicted the location of the P and NP I receptors in the tissue, the thickness of the tissue, and the value of the threshold strain for both receptor types. The predicted values agreed reasonably well with independent anatomical and physiological measurements.