Journal of Neurophysiology

Kutch, Jason J.; Kuo, Arthur D.; Bloch, Anthony M.; Rymer, William Z.

doi: 10.1152/jn.90274.2008pmid: 18799603

We developed a new approach to investigate how the nervous system activates multiple redundant muscles by studying the endpoint force fluctuations during isometric force generation at a multi-degree-of-freedom joint. We hypothesized that, due to signal-dependent muscle force noise, endpoint force fluctuations would depend on the target direction of index finger force and that this dependence could be used to distinguish flexible from synergistic activation of the musculature. We made high-gain measurements of isometric forces generated to different target magnitudes and directions, in the plane of index finger metacarpophalangeal joint abduction–adduction/flexion–extension. Force fluctuations from each target were used to calculate a covariance ellipse, the shape of which varied as a function of target direction. Directions with narrow ellipses were approximately aligned with the estimated mechanical actions of key muscles. For example, targets directed along the mechanical action of the first dorsal interosseous (FDI) yielded narrow ellipses, with 88% of the variance directed along those target directions. It follows the FDI is likely a prime mover in this target direction and that, at most, 12% of the force variance could be explained by synergistic coupling with other muscles. In contrast, other target directions exhibited broader covariance ellipses with as little as 30% of force variance directed along those target directions. This is the result of cooperation among multiple muscles, based on independent electromyographic recordings. However, the pattern of cooperation across target directions indicates that muscles are recruited flexibly in accordance with their mechanical action, rather than in fixed groupings. Address for reprint requests and other correspondence: J. Kutch, Ronald Tutor Hall, RTH-402, 3710 S. McClintock Ave., Los Angeles, CA 90089-2905 (E-mail: [email protected] )

Linares, Daniel; Holcombe, Alex O.

doi: 10.1152/jn.90682.2008pmid: 18753324

When humans view a moving object, the spatial lag in perception expected from neural delays may be partially corrected by motion mechanisms biasing perceived position. The drifting-Gabor illusion seems to support this view: the perceived location of a static envelope filled with a moving pattern is shifted in the direction of motion. To test whether this shifting mechanism also extrapolates the position of moving displacing objects, we compared the perceptual position shift for drifting versus displacing Gabors when the motion is toward the fovea and when the motion is away from the fovea. For displacing Gabors, the shift was much greater for motion toward the fovea, whereas for drifting Gabors, the shift was greater for motion away from the fovea. This dissociation suggests that the illusions are caused by different mechanisms. Address for reprint requests and other correspondence: D. Linares, Brennan MacCallum Bldg. (A18), Sydney NSW 2006, Australia (E-mail: [email protected] )

Gysin, Priska; Kaminski, Terry R.; Hass, Chris J.; Grobet, Cécile E.; Gordon, Andrew M.

doi: 10.1152/jn.90561.2008pmid: 18753327

In object transport during unimpeded locomotion, grip force is precisely timed and scaled to the regularly paced sinusoidal inertial force fluctuations. However, it is unknown whether this coupling is due to moment-to-moment predictions of upcoming inertial forces or a longer, generalized time estimate of regularly paced inertial forces generated during the normal gait cycle. Eight subjects transported a grip instrument during five walking conditions, four of which altered the gait cycle. The variations included changes in step length (taking a longer or shorter step) or stepping on and over a stable (predictable) or unstable (unpredictable support surface) obstacle within a series of baseline steps, which resulted in altered frequencies and magnitudes of the inertial forces exerted on the transported object. Except when stepping on the unstable obstacle, a tight temporal coupling between the grip and inertial forces was maintained across gait variations. Precision of this timing varied slightly within the time window for anticipatory grip force control possibly due to increased attention demands related to some of the step alterations. Furthermore, subjects anticipated variations in inertial force when the gait cycle was altered with increases or decreases in grip force, relative to the level of the inertial force peaks. Overall the maintenance of force coupling and scaling across predictable walking conditions suggests that the CNS is able to anticipate changes in inertial forces generated by gait variations and to efficiently predict the grip force needed to maintain object stability on a moment-to-moment basis. Address for reprint requests and other correspondence: A. M. Gordon, Dept of Biobehavioral Sciences, Teachers College, Columbia University, 525 W. 120th St., Box 199, New York, NY 10027 (E-mail: [email protected] )

Maruko, I.; Zhang, B.; Tao, X.; Tong, J.; Smith, E. L.; Chino, Y. M.

doi: 10.1152/jn.90397.2008pmid: 18753321

Macaque monkeys do not reliably discriminate binocular depth cues until about 8 wk of age. The neural factors that limit the development of fine depth perception in primates are not known. In adults, binocular depth perception critically depends on detection of relative binocular disparities and the earliest site in the primate visual brain where a substantial proportion of neurons are capable of discriminating relative disparity is visual area 2 (V2). We examined the disparity sensitivity of V2 neurons during the first 8 wk of life in infant monkeys and compared the responses of V2 neurons to those of V1 neurons. We found that the magnitude of response modulation in V2 and V1 neurons as a function of interocular spatial phase disparity was adult-like as early as 2 wk of age. However, the optimal spatial frequency and binocular response rate of these disparity sensitive neurons were more than an octave lower in 2- and 4-wk-old infants than in adults. Consequently, despite the lower variability of neuronal firing in V2 and V1 neurons of infant monkeys, the ability of these neurons to discriminate fine disparity differences was significantly reduced compared with adults. This reduction in disparity sensitivity of V2 and V1 neurons is likely to limit binocular depth perception during the first several weeks of a monkey's life. Address for reprint requests and other correspondence: Y. M. Chino, College of Optometry, Univ. of Houston, 505 J. Davis Armistead Bldg., Houston, TX 77204-2020 (E-mail: [email protected] )

Crow, Terry; Tian, Lian-Ming

doi: 10.1152/jn.90759.2008pmid: 18768639

Ciliary locomotion in the nudibranch mollusk Hermissenda is modulated by the visual and graviceptive systems. Components of the neural network mediating ciliary locomotion have been identified including aggregates of polysensory interneurons that receive monosynaptic input from identified photoreceptors and efferent neurons that activate cilia. Illumination produces an inhibition of type I i ( OFF -cell) spike activity, excitation of type I e ( ON -cell) spike activity, decreased spike activity in type III i inhibitory interneurons, and increased spike activity of ciliary efferent neurons. Here we show that pairs of type I i interneurons and pairs of type I e interneurons are electrically coupled. Neither electrical coupling or synaptic connections were observed between I e and I i interneurons. Coupling is effective in synchronizing dark-adapted spontaneous firing between pairs of I e and pairs of I i interneurons. Out-of-phase burst activity, occasionally observed in dark-adapted and light-adapted pairs of I e and I i interneurons, suggests that they receive synaptic input from a common presynaptic source or sources. Rhythmic activity is typically not a characteristic of dark-adapted, light-adapted, or light-evoked firing of type I interneurons. However, burst activity in I e and I i interneurons may be elicited by electrical stimulation of pedal nerves or generated at the offset of light. Our results indicate that type I interneurons can support the generation of both rhythmic activity and changes in tonic firing depending on sensory input. This suggests that the neural network supporting ciliary locomotion may be multifunctional. However, consistent with the nonmuscular and nonrhythmic characteristics of visually modulated ciliary locomotion, type I interneurons exhibit changes in tonic activity evoked by illumination. Address for reprint requests and other correspondence: T. Crow, Dept. of Neurobiology and Anatomy, Univ. of Texas Medical School, 6431 Fannin St., Houston, TX 77030 (E-mail: [email protected] )

Thompson, Aidan A.; Henriques, Denise Y. P.

doi: 10.1152/jn.90599.2008pmid: 18768640

Remembered object locations are stored in an eye-fixed reference frame, so that every time the eyes move, spatial representations must be updated for the arm-motor system to reflect the target's new relative position. To date, studies have not investigated how the brain updates these spatial representations during other types of eye movements, such as smooth-pursuit. Further, it is unclear what information is used in spatial updating. To address these questions we investigated whether remembered locations of pointing targets are updated following smooth-pursuit eye movements, as they are following saccades, and also investigated the role of visual information in estimating eye-movement amplitude for updating spatial memory. Misestimates of eye-movement amplitude were induced when participants visually tracked stimuli presented with a background that moved in either the same or opposite direction of the eye before pointing or looking back to the remembered target location. We found that gaze-dependent pointing errors were similar following saccades and smooth-pursuit and that incongruent background motion did result in a misestimate of eye-movement amplitude. However, the background motion had no effect on spatial updating for pointing, but did when subjects made a return saccade, suggesting that the oculomotor and arm-motor systems may rely on different sources of information for spatial updating. Address for reprint requests and other correspondence: D. Henriques, School of Kinesiology and Health Science, York University, 4700 Keele Street, Toronto, ON, Canada M3J 1P3 (E-mail: [email protected] )

Steigerwald, F.; Pötter, M.; Herzog, J.; Pinsker, M.; Kopper, F.; Mehdorn, H.; Deuschl, G.; Volkmann, J.

doi: 10.1152/jn.90574.2008pmid: 18701754

We recorded resting-state neuronal activity from the human subthalamic nucleus (STN) during functional stereotactic surgeries. By inserting up to five parallel microelectrodes for single- or multiunit recordings and applying statistical spike-sorting methods, we were able to isolate a total of 351 single units in 65 patients with Parkinson's disease (PD) and 33 single units in 9 patients suffering from essential tremor (ET). Among these were 93 pairs of simultaneously recorded neurons in PD and 17 in ET, which were detected either by the same ( n = 30) or neighboring microelectrodes ( n = 80). Essential tremor is a movement disorder without any known basal ganglia pathology and with normal dopaminergic brain function. By comparing the neuronal activity of the STN in patients suffering from PD and ET we intended to characterize, for the first time, changes of basal ganglia activity in the human disease state that had previously been described in animal models of Parkinson's disease. We found a significant increase in the mean firing rate of STN neurons in PD and a relatively larger fraction of neurons exhibiting burstlike activity compared with ET. The overall proportion of neurons exhibiting intrinsic oscillations or interneuronal synchronization as defined by significant spectral peaks in the auto- or cross-correlations functions did not differ between PD and ET when considering the entire frequency range of 1–100 Hz. The distribution of significant oscillations across the theta (1–8 Hz), alpha (8–12 Hz), beta (12–35 Hz), and gamma band (>35 Hz), however, was uneven in ET and PD, as indicated by a trend in Fisher's exact test ( P = 0.05). Oscillations and pairwise synchronizations within the 12- to 35-Hz band were a unique feature of PD. Our results confirm the predictions of the rate model of Parkinson's disease. In addition, they emphasize abnormalities in the patterning and dynamics of neuronal discharges in the parkinsonian STN, which support current concepts of abnormal motor loop oscillations in Parkinson's disease. Address for reprint requests and other correspondence: J. Volkmann, Department of Neurology, Christian-Albrechts-Universität Kiel, Schittenhelmstr. 10, D-24105 Kiel, Germany (E-mail: [email protected] )

Duch, Carsten; Vonhoff, Fernando; Ryglewski, Stefanie

doi: 10.1152/jn.90758.2008pmid: 18715893

Dendrites are the fundamental determinant of neuronal wiring. Consequently dendritic defects are associated with numerous neurological diseases and mental retardation. Neuronal activity can have profound effects on dendritic structure, but the mechanisms controlling distinct aspects of dendritic architecture are not fully understood. We use the Drosophila genetic model system to test the effects of altered intrinsic excitability on postembryonic dendritic architecture development. Targeted dominant negative knock-downs of potassium channel subunits allow for selectively increasing the intrinsic excitability of a selected subset of motoneurons, whereas targeted expression of a genetically modified noninactivating potassium channel decrease intrinsic excitability in vivo. Both manipulations cause significant dendritic overgrowth, but by different mechanisms. Increased excitability causes increased dendritic branch formation, whereas decreased excitability causes increased dendritic branch elongation. Therefore dendritic branching and branch elongation are controlled by separate mechanisms that can be addressed selectively in vivo by different manipulations of neuronal intrinsic excitability. Address for reprint requests and other correspondence: C. Duch, School of Life Sciences, Arizona State University, Tempe, AZ 85287 (E-mail: [email protected] )

Zarahn, Eric; Weston, Gregory D.; Liang, Johnny; Mazzoni, Pietro; Krakauer, John W.

doi: 10.1152/jn.90529.2008pmid: 18596178

Adaptation of the motor system to sensorimotor perturbations is a type of learning relevant for tool use and coping with an ever-changing body. Memory for motor adaptation can take the form of savings: an increase in the apparent rate constant of readaptation compared with that of initial adaptation. The assessment of savings is simplified if the sensory errors a subject experiences at the beginning of initial adaptation and the beginning of readaptation are the same. This can be accomplished by introducing either 1 ) a sufficiently small number of counterperturbation trials (counterperturbation paradigm CP ) or 2 ) a sufficiently large number of zero-perturbation trials (washout paradigm WO ) between initial adaptation and readaptation. A two-rate, linear time-invariant state-space model (SSM LTI,2 ) was recently shown to theoretically produce savings for CP . However, we reasoned from superposition that this model would be unable to explain savings for WO . Using the same task (planar reaching) and type of perturbation (visuomotor rotation), we found comparable savings for both CP and WO paradigms. Although SSM LTI,2 explained some degree of savings for CP it failed completely for WO . We conclude that for visuomotor rotation, savings in general is not simply a consequence of LTI dynamics. Instead savings for visuomotor rotation involves metalearning, which we show can be modeled as changes in system parameters across the phases of an adaptation experiment. Address for reprint requests and other correspondence: E. Zarahn, Motor Performance Laboratory, The Neurological Institute, New York, NY 10032 (E-mail: [email protected] )

Johnson, Matthew D.; McIntyre, Cameron C.

doi: 10.1152/jn.90372.2008pmid: 18768645

Deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) is an effective therapy option for controlling the motor symptoms of medication-refractory Parkinson's disease and dystonia. Despite the clinical successes of GPi DBS, the precise therapeutic mechanisms are unclear and questions remain on the optimal electrode placement and stimulation parameter selection strategies. In this study, we developed a three-dimensional computational model of GPi-DBS in nonhuman primates to investigate how membrane channel dynamics, synaptic inputs, and axonal collateralization contribute to the neural responses generated during stimulation. We focused our analysis on three general neural elements that surround GPi-DBS electrodes: GPi somatodendritic segments, GPi efferent axons, and globus pallidus pars externa (GPe) fibers of passage. During high-frequency electrical stimulation (136 Hz), somatic activity in the GPi showed interpulse excitatory phases at 1–3 and 4–5.5 ms. When including stimulation-induced GABA A and AMPA receptor dynamics into the model, the somatic firing patterns continued to be entrained to the stimulation, but the overall firing rate was reduced (78.7 to 25.0 Hz, P < 0.001). In contrast, axonal output from GPi neurons remained largely time-locked to each pulse of the stimulation train. Similar entrainment was also observed in GPe efferents, a majority of which have been shown to project through GPi en route to the subthalamic nucleus. The models suggest that pallidal DBS may have broader network effects than previously realized and the modes of therapy may depend on the relative proportion of GPi and/or GPe efferents that are directly affected by the stimulation. Address for reprint requests and other correspondence: C. C. McIntyre, Department of Biomedical Engineering, Cleveland Clinic Foundation, 9500 Euclid Avenue, ND20, Cleveland, OH, 44195 (E-mail: [email protected] )