Primary motor cortex neuronal discharge during reach-to-grasp: controlling the hand as a unit.

This study has begun to test the hypothesis that aspects of hand/object shape are represented in the discharge of primary motor cortex (M1) neurons. Two monkeys were trained in a visually cued reach-to-grasp task, in which object properties and grasp forces were systematically varied. Behavioral analyses show that the reach and grasp force production were constant across the objects. The discharge of M1 neurons was highly modulated during the reach and grasp. Multiple linear regressions models revealed that the M1 discharge was highly dependent on the object grasped, with object class, volume, orientation and grasp force as significant predictors. These findings are interpreted as evidence that the CNS controls the hand as a unit.

Central processes for the multiparametric control of arm movements in primates.

Recent single-unit recording studies have clarified how multiple parameters of movement are signaled by individual cortical and cerebellar neurons, and also that multiple coordinate frames are utilized. Cognitive processes also modulate the firing of these neurons. The various signals and coordinate systems vary in time and evolve throughout a behavioral sequence, consistent with the demands of the task and the required sensorimotor transformations.

Hand synergies during reach-to-grasp.

An emerging viewpoint is that the CNS uses synergies to simplify the control of the hand. Previous work has shown that static hand postures for mimed grasps can be described by a few principal components in which the higher order components explained only a small fraction of the variance yet provided meaningful information. Extending that earlier work, this study addressed whether the entire act of grasp can be described by a small number of postural synergies and whether these synergies are similar for different grasps. Five right-handed adults performed five types of reach-to-grasps including power grasp, power grasp with a lift, precision grasp, and mimed power grasp and mimed precision grasp of 16 different objects. The object shapes were cones, cylinders, and spindles, systematically varied in size to produce a large range of finger joint angle combinations. Three-dimensional reconstructions of 21 positions on the hand and wrist throughout the reach-to-grasp were obtained using a four-camera video system. Singular value decomposition on the temporal sequence of the marker positions was used to identify the common patterns ("eigenpostures") across the 16 objects for each task and their weightings as a function of time. The first eigenposture explained an average of 97.3 +/- 0.89% (mean +/- SD) of the variance of the hand shape, and the second another 1.9 +/- 0.85%. The first eigenposture was characterized by an open hand configuration that opens and closes during reach. The second eigenposture contributed to the control of the thumb and long fingers, particularly in the opening of the hand during the reach and the closing in preparation for object grasp. The eigenpostures and their temporal evolutions were similar across subjects and grasps. The higher order eigenpostures, although explaining only small amounts of the variance, contributed to the movements of the fingers and thumb. These findings suggest that much of reach-to-grasp is effected using a base posture with refinements in finger and thumb positions added in time to yield unique hand shapes.

Studies of binaural detection in the rabbit (Oryctolagus cuniculus) with Pavlovian conditioning.

A Pavlovian conditioned eyeblink response in rabbits (Oryctolagus cuniculus) was used to study psychoacoustical phenomena previously demonstrated in human listeners and other animals. This article contains the results of a tone-in-noise detection study to examine 2 psychoacoustical phenomena in rabbit and in human listeners: (a) the binaural masking level difference (BMLD) and (b) differential performance across reproducible noise masker waveforms. The rabbits demonstrated a BMLD comparable in size to other species. Significant differences in performance across reproducible noise masker waveforms were seen in the rabbits. This performance was compared with the performance of human listeners using the same set of waveforms.

Release from masking due to spatial separation of sources in the identification of nonspeech auditory patterns.

A nonspeech pattern identification task was used to study the role of spatial separation of sources on auditory masking in multisource listening environments. The six frequency patterns forming the signal set were comprised of sequences of eight 60-ms tone bursts. Bursts of masking sounds were played synchronously with the signals. The main variables in the study were (1) the difference in spatial separation in the horizontal plane between signals and maskers and (2) the nature of the masking produced by the maskers. Spatial separation of signal and masker ranged from 0-180 degrees. The maskers were of two types: (1) a sequence of eight 60-ms bursts of Gaussian noise intended to produce predominantly peripherally based "energetic masking" and (2) a sequence of eight 60-ms bursts of eight-tone complexes intended to produce primarily centrally based "informational masking." The results indicated that identification performance improved with increasing separation of signal and masker. The amount of improvement depended upon the type of masker and the center frequency of the signal patterns. Much larger improvements were found for spatial separation of the signal and informational masker than for the signal and energetic masker. This was particularly apparent when the acoustical advantage of the signal-to-noise ratio in the more favorable of the two ears (the ear nearest the signal) was taken into account. The results were interpreted as evidence for an important role of binaural hearing in reducing sound source or message uncertainty and may contribute toward solving the "cocktail party problem."

Temporal profile of the directional tuning of the discharge of dorsal premotor cortical cells.

This study examined the directional modulation of dorsal premotor (PMd) cells as a function of time in an instructed delay, reaching task that systematically varied direction and accuracy constraints. In two monkeys, the activity of 150 PMd cells was recorded and the preferred direction (PD) of the firing as a function of time, the PD trajectory, was calculated. Forty-one cells had nearly continuous significant directional tuning of at least 1 s duration (mean duration 1694 +/- 754 ms) that began in the instructed delay period and continued into the movement period. The PD gradually changed in time (mean change of 47.7 +/- 40.8 degrees), a change best described as a rotation. The change in the directional tuning as a function of time is consistent with the hypothesis that the PMd plays a role in the non-standard mapping of sensory stimuli into motor commands.

Organization of reaching and grasping movements in the primate cerebellar nuclei as revealed by focal muscimol inactivations.

Two monkeys were trained to point to targets and to retrieve fruit bits from a Kluver board, bottles, and tubes. Once proficient in the tasks, the macaques underwent aseptic surgical implantation of a recording chamber over the cerebellar nuclei on the side of their preferred hand. After recovery from surgery, a series of mapping penetrations were completed to identify task-related areas within the cerebellar nuclei. Muscimol (4- 16 microgram; 1-2 microgram/microliter) was pressure injected at different sites within the forelimb zone, and the resultant deficits were observed as the monkeys performed the behavioral tasks. Quantitative measures of task performance were supplemented by direct observation of live and videotaped performance. The locations of nuclear inactivation sites were reconstructed from marking lesions and tracks visible in histological sections. Injections placed in the cerebellar interpositus nucleus and adjacent regions of dentate caused a variety of deficits in forelimb function. A prominent anteroposterior specialization was apparent within the forelimb zone of this intermediate nuclear region. Injections into the anterior interpositus nucleus and adjacent dentate impaired preshaping of the hand and the manipulation of objects, whereas injections placed more posteriorly in posterior interpositus nucleus and adjacent dentate produced deficits in the aiming of reach and the stability of the arm. During anterior injections, the monkeys failed to adequately extend their fingers in preparation for target contact, as documented for >85% of the reaches in the pointing task of monkey J. Up to 38% of the fruit bits it attempted to retrieve from the Kluver board were dropped. In comparison, during posterior inactivations, 15% were dropped and during control conditions 3% were dropped. The monkeys made significantly greater pointing errors during posterior inactivations (11 times for monkey J and 4 times for monkey C) than during anterior inactivations (8 times for monkey J and 2 times for monkey C). We refer to the region producing hand deficits as the anterior hand zone and the region producing reaching deficits as the posterior reach zone. These results are discussed in relation to the problem of achieving spatiotemporal coordination in the large population of nuclear cells that participate in any given movement. The results do not favor the hypothesis that coordination is achieved through a selection of Purkinje cells along beams of parallel fibers. Instead, it is proposed that distal and proximal musculature is coordinated by the adaptive influences of climbing fiber input to Purkinje cells. We envision a relatively nonspecific recruitment of anterior and posterior nuclear cells due to positive feedback in the limb premotor network, which then is shaped into an appropriate spatiotemporal pattern of discharge through the inhibitory input from Purkinje cells.

Movement kinematics encoded in complex spike discharge of primate cerebellar Purkinje cells.

Monkeys performed a multijoint arm-reaching task that systematically varied movement direction and distance. Purkinje cell activity was recorded from 231 task-related cells, and the complex spike discharge was analyzed in relation to distance and direction. The complex spike activity of 123 Purkinje cells changed significantly relative to the background rate. Of these 123, the activity of 85 cells was related to distance and/or direction. The complex spike activity of 54 of these 85 cells fitted a cosine tuning curve for direction, generally at one distance. Using a simple linear regression model, the complex spike activity of 56 cells was significantly correlated with movement distance, usually in one direction. We conclude that the complex spike discharge of Purkinje cells is spatially tuned and strongly related to movement kinematics.

Analysis of polymorphisms of the 2',3'-cyclic nucleotide-3'-phosphodiesterase gene in patients with multiple sclerosis.

Susceptibility to multiple sclerosis (MS) is widely held to have a genetic component. Possible candidate genes conferring this susceptibility include those coding for proteins specific to central nervous system (CNS) myelin. 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) is an enzyme found at high concentrations in CNS myelin, however its function is unknown. The amino acid sequence of CNPase shows a C-terminal motif characteristic of proteins involved in signal transduction pathways, suggesting a key role in myelin function. We have analysed the entire expressed sequence of the human CNPase gene in patients with multiple sclerosis and in healthy controls using single strand conformation polymorphism (SSCP) analysis. Nine previously undescribed mutations were detected, most of these occurred with equal frequency in both groups. However, a T-->C transition at nucleotide position 4306 in the region of the gene coding for the 3' untranslated region of the mature mRNA was found in a homozygous form in two out of 54 patients but in none of 100 controls. While the significance of this is unclear, it would appear unlikely that mutations in the expressed regions of the human CPNase gene contribute to genetic susceptibility to MS in the majority of sufferers.

Binaural advantage for sound pattern identification.

Listeners were trained to identify six patterns of eight sequentially presented 48-ms tone bursts. The variation in frequency forming the patterns was confined to a relatively narrow range around the nominal center frequency, which was either 500, 1000, or 3000 Hz, or was selected randomly on each presentation from a range of 450-3300 Hz. Detection (500 and 3000 Hz only) and identification of the six patterns masked by Gaussian noise was measured in two interaural presentation conditions: masker in-phase and signal in-phase (NoSo), and masker in-phase and signal pi rad out-of-phase (NoS pi). The differences in performance in the two interaural presentation conditions for detection and identification are referred to as "masking-level differences" (MLDs) and "identification-level differences" (IDLDs), respectively. At 500 Hz, MLDs and IDLDs were about 11-13 dB. At 3000 Hz, the MLDs and IDLDs were about 1-3 dB. For the random-center-frequency condition, the slopes of the identification-level functions were much shallower for the NoS pi condition than for the NoSo condition so the binaural advantage was large at low signal-to-noise ratios and declined as signal-to-noise ratio increased. This finding was due to the broad frequency range over which the information was distributed and the decline in the binaural advantage with increasing frequency, a conclusion consistent with that reported for the binaural advantage for speech intelligibility. A second experiment demonstrated that MLDs and IDLDs could be manipulated independently: A 500-Hz tone was added to each element of the 3000-Hz patterns. A large MLD was found--due to detection of the 500-Hz tone--while the identification-level functions were determined solely by the high-frequency information, which produced small IDLDs. Finally, the Gaussian noise masker was replaced by an informational masker comprised of eight randomly chosen eight-tone bursts played simultaneously with the signal-pattern elements which were centered at 1000 Hz. Large amounts of informational masking were found for identification. The slopes of the identification-level functions were much shallower than found for the Gaussian noise masker and a relatively small binaural advantage (about 5 dB) was observed.

Single strand conformation analysis of two genes contained within the first intron of the neurofibromatosis type I gene in patients with multiple sclerosis.

Single strand conformation analysis has become the most widely used technique to screen large numbers of DNA samples for unknown mutations which may contribute to genetic susceptibility to disease. The method relies on the electrophoretic migration of a single strand of nucleic acid in a polyacrylamide gel being dependent on its conformation which is in turn dependent on its sequence. We have examined two closely related genes present in the first intron of the neurofibromatosis type I gene--the oligodendrocyte myelin glycoprotein (OMGP) gene and the ecotropic viral integration 2A (EVI2A) gene--in 36 patients with multiple sclerosis (MS) and 36 healthy controls. A single mutation was found in the OMGP gene which resulted in an amino-acid change of glycine to aspartic acid. This occurred in identical proportions (16.6%) in MS patients and controls. Two rare mutations were found in the EVI2A gene, one resulting in an arginine substituting for a glutamine (one control and one patient), the other in the replacement of a glycine with serine (one control only). A third common polymorphism was seen in 5'-untranslated region of the EVI2A gene, with 65% of patients and controls showing a T-->C transition in either a heterozygous or a homozygous form. This makes it unlikely that either of these genes is involved in genetic susceptibility to MS, but regions of these genes outside of the exonic sequences have not been examined.

Discriminating coherence in spectro-temporal patterns.

This study examined the ability of trained listeners to discriminate coherent components in randomly varying spectral patterns. In each observation interval, the listener was presented with a sequence of bursts of multitone complexes having a fixed number of tones (m) in each burst. In the standard interval, the frequency of each tone in every burst was chosen randomly between 200 and 5000 Hz. In the signal interval, the frequencies of n tones were repeated throughout the burst sequence while the remaining m-n tones were chosen at random. The n tones were coherent in the sense that they were perceived as "sticking together" to form a pattern. The listener's task was to discriminate which burst sequence contained the n components. The results indicated that discrimination improved with increasing n/m, with increasing number of bursts per interval, and declined as the coherent components were increasingly perturbed in frequency. Further, for a fixed value of the ratio n/m discriminability was relatively independent of m. A model incorporating multichannel filtering and an optimum decision rule was reasonably successful in accounting for the experimental results.

Reducing informational masking by sound segregation.

Informational masking was reduced using three stimulus presentation schemes that were intended to perceptually segregate the signal from the masker. The maskers were sets of sinusoids chosen randomly in frequency and intensity on each stimulus interval or, in some conditions, on every masker burst in a series of bursts within intervals. Masker components were excluded from the frequency region surrounding the 1000-Hz signal to minimize the energetic masking. Masked thresholds as great as 60-70 dB above quiet threshold were observed for some subjects in some conditions. It was shown that this informational masking could be reduced as much as 40 dB by: (1) presenting the masker to both ears and signal to one ear; (2) playing different masker samples sequentially in each interval of every trial; or (3) presenting the signal in alternate bursts of multiple, identical masker samples. For the binaural manipulation, informational masking was reduced because the masker and signal were perceived as originating from different interaural locations. In the latter two manipulations, a difference in the spectral or temporal pattern of the signal and masker provided the detection cue. These effects were interpreted as evidence of the importance of perceptual segregation of sounds in noisy listening environments where signal reception is not limited by energetic masking.

Auditory detection of the human brainstem auditory evoked response.

The human brainstem auditory evoked response (BAER) is a far-field electrical potential recorded from the scalp in response to transient acoustic stimuli. Typically, voltage measurements are obtained for a period of about 10 msec following the acoustic stimulus, which is repeated and summed several hundred or thousand times to permit extraction of the response from ongoing nonauditory neural activity. The judgment about whether a response has been obtained is normally based on the pattern observed in a visual display of the waveform. In this study, we investigated whether listeners can distinguish BAERs elicited by acoustic clicks from control waveforms obtained with no acoustic stimulus when the waveforms were presented auditorily. For this purpose, BAER and control waveforms were transduced by an earphone and used in an auditory detection task. Several presentation strategies were examined, including lengthening the waveform by playing it at a lower sampling rate, playing the waveform repetitively, and using the waveform to frequency modulate a pure-tone carrier. The results indicated that the BAER, when extended in duration and used to frequency modulate a 1000-Hz pure tone, was highly detectable in a YES-NO paradigm for BAERs elicited with high-level (e.g., 70 dB re. behavioral detection threshold) acoustic clicks. Performance declined to near chance as the level of the BAER-eliciting stimulus was lowered to 10 dB. In general, detection performance for stimuli presented visually was slightly, but consistently, superior to that which occurred for stimuli presented auditorily.

Discriminability of narrow-band sounds in the absence of level cues.

Several experiments are described in which the task of the observer was to detect an intensity increment to the center tone of a narrow-band, multitone complex. The sound-pressure levels of the stimuli were equated, then randomized, so that listeners could not detect the signal by using level cues. The primary experimental variables were the number of tones in the masker spectrum, the level of the center tone or "pedestal" relative to the other tones, the center frequency and the sound-pressure level. Both "random-phase" and "fixed-phase" conditions (referring to whether the pattern of starting phases of the nonsignal tones was chosen randomly on every presentation or was held constant throughout each trial and block of trials) were tested. Although no simple detection strategy appeared to account for all of the results, the most plausible explanation for performance in most conditions was that the listeners were able to discriminate between sounds based on subtle differences in the amplitude envelopes of the waveforms.

A new technique for measuring spectral shape discrimination.

A new technique is described for studying the ability of listeners to discriminate between sounds on the basis of spectral shape, a process called "auditory profile analysis." The advantage of the technique is that it reduces the range of the random rove in level necessary to provide a specified limit on the performance which listeners could achieve by "level detection;" that is, by employing a detection strategy based solely on comparisons of stimulus level. Thresholds were measured for the just-discriminable "ripple" (a pattern of alternating intensity increments and decrements) in an equal-amplitude, multitone reference spectrum for a group of normal-hearing listeners. Broadband, high-pass and low-pass filtered conditions were tested. The results indicated that the thresholds obtained using the new technique were well below the lowest level achievable by level detection (referred to as the "level-detection limit") in all conditions using a 20-dB random within-trial rove in overall level. The lowest threshold occurred for the broadband stimulus while the highest threshold was observed for the most extreme high-pass filtered condition. The new technique appears to be well-suited for study of profile analysis in hearing-impaired listeners where stimulus bandwidth and rove range are limited.

Evaluation of simple models of auditory profile analysis using random reference spectra.

This article describes further study of the finding reported by Green et al. [J. Acoust. Soc. Am. 73, 639-643 (1983)] and others that, in certain conditions, the threshold of detectability for an intensity increment to the center tone of a multitone reference spectrum decreased as the number of nonsignal tones increased. That result was considered remarkable since critical-band theory would predict that these nonsignal tones, spaced outside the "critical band" containing the signal, would have no effect on or, at most, slightly decrease within-band detectability--and certainly could not account for the result of improved detectability found in the study cited above. Recently, Henn and Turner [J. Acoust. Soc. Am. 88, 126-131 (1990)] were unable to replicate the result described above, concluding that the phenomenon exists only in "limited conditions" and that is "highly individual" in nature. Further, they speculated that the most likely reason for the discrepancy between their study and previous studies was the selection and/or training of the observers. The present study addressed the effects of the amount of subject training on the finding of Green et al. while controlling the potential effects of stimulus order. Specifically, for a group of three "naive" listeners, thresholds were measured for 3-, 7-, and 21-tone inharmonic complexes as a function of the amount of practice in a mixed-block design. In all cases the group mean thresholds decreased as the number of nonsignal tones increased both initially and after extensive practice for both fixed- and roving-level conditions. Thus the effect does not appear to be an artifact of the amount or order of training subjects receive. The possible role of subject sample size and the magnitude of individual differences in obtaining the effect remains an open question. Two hypotheses suggested to account for the improvement in threshold with increasing number of nonsignal tones were evaluated. The hypotheses were represented by simple mathematical models, referred to as the "multiple-comparison" and "pitch-cue" models. The predictions of both models were compared with the results of a series of detection experiments in which the independent variables were the number of nonsignal tones and amount of random, within-trial "amplitude perturbation" [cf. Kidd et al., J. Acoust. Soc. Am. 79, 1045-1053 (1986)] of the nonsignal tones. Neither model, as applied, provided a satisfactory account of the effects of the main variables of number of tones and amount of perturbation.(ABSTRACT TRUNCATED AT 400 WORDS)

Roving-level tone-in-noise detection.

The detectability of tones, or of intensity increments to tones, in bands of random noise was measured for conditions in which the overall level was fixed or was randomly roved from interval to interval of every experimental trial. The purpose of the within-trial rove was to limit the usefulness of a detection strategy based on overall level or level within a single "critical band." At "supracritical" bandwidths, the functions relating masked threshold to noise bandwidth for the roved conditions were similar to those obtained when no rove was employed. At "subcritical" bandwidths, thresholds were higher in some roved conditions, but, for the largest rove, were still lower than would be predicted from arguments based purely on level detection--with one exception. A comparison of observer performance relative to the statistical limits imposed by the roving-level procedure indicated that the traditional critical-band energy-detector model could not account for the results, which are attributed to discrimination based on spectral shape or on waveshape.

Effects of optokinetic velocity and medial vestibulo-cerebellum lesions on vestibulo-ocular reflex direction adaptation in the cat.

Adaptive horizontal vestibulo-ocular reflex eye movements in response to vertical (pitch) rotations were produced by exposing three cats to synchronized horizontal optokinetic and vertical vestibular oscillations at 0.25 Hz. The effects of optokinetic stimulus velocity (6-80 degrees/s peak) and nodulo-uvular cerebellum lesions were studied. All optokinetic velocities elicited vestibulo-ocular reflex direction adaptation. though 6 degrees/s stimuli were somewhat less effective. Restricted aspirations of cerebellar vermis lobules IX and X in two cats resulted in reduced but still clearly evident adaptation.

Evidence for sensory-trace comparisons in spectral shape discrimination.

The ability of experienced observers to discriminate changes in the shapes of complex sound spectra was studied for three conditions. In one condition, the reference spectrum or "background" was fixed in spectral shape across each block of trials; in a second condition, the reference spectrum differed in spectral shape from trial to trial within each block of trials but was the same for the two presentations within a trial; and, in a third condition, the reference spectrum differed in spectral shape on every stimulus presentation. The variation in the reference spectrum was a random perturbation in the amplitudes of the tonal components comprising the complex sounds. The signal was an intensity increment to the center component (1000 Hz) of the complex and was present in one interval of each two-interval, two-alternative, forced-choice trial. The principal experimental manipulations were the degree of amplitude perturbation of the reference spectrum and the interval of time between the two stimulus presentations of each trial (interstimulus interval, ISI). The theory proposed by Durlach and Braida [J. Acoust. Soc. Am. 46, 372-383 (1969)] describing memory processes involved in the perception of sound intensity was used to explain the experimental results. As that theory was applied in this study, only the condition in which the stimuli were perturbed between trials showed evidence for comparisons based on "sensory traces," while the conditions in which the stimuli were fixed or were perturbed within trials were best explained by comparisons based on judgments relative to the stimulus context.