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Biomedical subjects

J R Wolpaw

Publications and source records attributed to J R Wolpaw.

At least 19 recordsLinked to original sources

Constancy of motor axon conduction time during growth in rats.

Axon conduction distance, conduction velocity, and conduction time were measured for individual triceps surae motoneurons in Sprague-Dawley rats weighing 230-630 g (i.e., age range 6-16 weeks). Both conduction distance (nerve length) and velocity were closely correlated with weight (r = 0.95 and r = 0.82, respectively). In contrast, conduction time did not change as weight increased nearly threefold. This striking constancy is probably due to a corresponding increase in axon diameter. It could contribute to maintenance of stable motor performance during rapid growth.

Animals

An EEG-based brain-computer interface for cursor control.

This study began development of a new communication and control modality for individuals with severe motor deficits. We trained normal subjects to use the 8-12 Hz mu rhythm recorded from the scalp over the central sulcus of one hemisphere to move a cursor from the center of a video screen to a target located at the top or bottom edge. Mu rhythm amplitude was assessed by on-line frequency analysis and translated into cursor movement: larger amplitudes moved the cursor up and smaller amplitudes moved it down. Over several weeks, subjects learned to change mu rhythm amplitude quickly and accurately, so that the cursor typically reached the target in 3 sec. The parameters that translated mu rhythm amplitudes into cursor movements were derived from evaluation of the distributions of amplitudes in response to top and bottom targets. The use of these distributions was a distinctive feature of this study and the key factor in its success. Refinements in training procedures and in the distribution-based method used to translate mu rhythm amplitudes into cursor movements should further improve this 1-dimensional control. Achievement of 2-dimensional control is under study. The mu rhythm may provide a significant new communication and control option for disabled individuals.

Adult

Operantly conditioned plasticity in spinal cord.

Recent work has shown that the monosynaptic pathway of the SSR can be operantly conditioned, and that a significant part of the plasticity responsible for the behavioral change resides in the spinal cord. The most likely sites of this activity-driven plasticity are the synapse of the Ia afferent neuron on the motoneuron and/or the motoneuron itself. Because the SSR pathway is the simplest and most accessible stimulus-response pathway in the vertebrate CNS, it may provide a valuable experimental model for elucidating activity-driven CNS changes responsible for learning.

Animals

Operant conditioning of H-reflex in freely moving monkeys.

The H-reflex, the electrical analog of the stretch reflex or tendon jerk, is the simplest behavior of the primate CNS. It is subserved by a wholly spinal two-neuron reflex arc. Recent studies show that this reflex can be increased or decreased by operant conditioning, and that such conditioning causes plastic changes in the spinal cord itself. Thus, H-reflex conditioning provides a powerful new model for investigating primate memory traces. The key feature of this model, the conditioning task, originally required animal restraint. This report describes a new tether-based design that allows H-reflex measurement and conditioning without restraint. This design integrates the conditioning task into the life of the freely moving animal.

Animals

Memory traces in spinal cord.

The complexity and inaccessibility of the vertebrate CNS impede the localization and description of memory traces and the definition of the processes that create them. Recent work has shown that the spinal stretch reflex (SSR), which is produced by a monosynaptic two-neuron pathway, can be operantly conditioned, and that memory traces responsible for this behavioral change reside in the spinal cord. The probable locations are the terminal of the Ia affernt neuron on the motoneuron and/or the motoneuron itself. Because it modifies a simple well-defined and accessible pathway, SSR conditioning may be a valuable experimental model for studying vertebrate memory.

Animals

Memory traces in spinal cord produced by H-reflex conditioning: effects of post-tetanic potentiation.

Operant conditioning of the wholly spinal, largely monosynaptic triceps surae H-reflex in monkeys causes changes in lumbosacral spinal cord that persist after removal of supraspinal influence. We evaluated the interaction between post-tetanic potentiation and these memory traces. Animals in which the triceps surae H-reflex in one leg had been increased or decreased by conditioning were deeply anesthetized, and monosynaptic reflexes to L6-S1 dorsal root stimulation were recorded before and after tetanization from both legs for 3 days after thoracic cord transection. Animals remained anesthetized throughout and were sacrificed by overdose. Reflex asymmetries consistent with the effect of H-reflex conditioning were present after transection and persisted through the 3 days of study. Tetanization affected conditioned leg and control leg reflexes similarly. This finding suggests that, while post-tetanic potentiation and probably H-reflex conditioning alter Ia synaptic transmission, the two phenomena have different mechanisms.

Animals

Chronic exposure of primates to 60-Hz electric and magnetic fields: I. Exposure system and measurements of general health and performance.

We exposed pigtailed macaques (Macaca nemestrina) to electric (E) and magnetic (B) fields at strengths of 3 kV/m and 0.1 G, 10 kV/m and 0.3 G, and 30 kV/m and 0.9 G for three 21 day segments. These three exposure segments were preceded and followed by 21 day sham exposure segments. Additional animals received only sham exposure for five 21 day segments. Detailed description of the exposure chamber and field generation apparatus is given. We evaluated measures of animal well-being, including weight, blood chemistry, blood cell counts, and performance on a simple motor task, and performed postmortem examinations. Reliable and consistent results were obtained throughout data collection. None of the measures evaluated was significantly affected by E- and B-field exposures. Data obtained during actual exposure segments were not distinguishable from those obtained during the initial and final sham exposure segments, nor were they different from data obtained from the sham-exposed animals. Thus, field exposure had no apparent effects on general health or performance.

Animals

Chronic exposure of primates to 60-Hz electric and magnetic fields: II. Neurochemical effects.

We exposed Macaca nemestrina (pig-tailed macaques) to electric (E) and magnetic (B) fields ranging in intensity from 3 kV/m and 0.1 G to 30 kV/m and 0.9 G for three 21-day (d) periods. Experimental animals were exposed to sham E and B fields for two 21-d periods, one prior to and one following actual exposure to E and B fields, resulting in a total of five 21-d periods. Control animals were exposed to sham E and B fields for the entire 105-d interval. At the end of each 21-d period cerebrospinal fluid (CSF) was obtained by lumbar puncture and analyzed for concentrations of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), metabolites of dopamine and serotonin neurotransmitters, respectively, by high-performance liquid chromatography with electrochemical detection (HPLC-ECD). Results are based on an examination of six experimental and four control animals. Exposure to E and B fields at all strengths was associated with a significant decline in CSF concentrations of both HVA and 5-HIAA when statistical comparisons were made against values obtained at the end of the preexposure interval. However, HVA returned to preexposure levels during the postexposure period, while 5-HIAA did not. No significant change in the concentrations of HVA or 5-HIAA was noted in the control animals. These results strongly suggest that exposure of the nonhuman primate to E and B fields can significantly affect specific biochemical estimates of nervous system function. These effects may involve alterations either in neuronal activity or in the activity of enzymes that catabolize the neurotransmitters.

Animals

Chronic exposure of primates to 60-Hz electric and magnetic fields: III. Neurophysiologic effects.

The neurophysiologic effects of combined 60-Hz electric (E) and magnetic (B) fields, of magnitudes comparable to those produced by high-voltage powerlines, were investigated in 10 monkeys (Macaca nemestrina). Six animals (experimental group) were each exposed to three different levels of E and B fields: 3 kV/m and 0.1 G, 10 kV/m and 0.3 G, and 30 kV/m and 0.9 G. Field exposures were preceded and followed by sham exposures, during which factors of field generation were present (e.g., heat, vibration, noise, etc.) without E and B fields. Each of the five segments (i.e., the three exposure segments and the initial and final sham exposure segments) lasted 3 weeks. Animals were exposed for 18 h/day (fields on at 1600 h, off at 1000 h). Four other animals (external control group) were given sham exposure for the entire 15-week period. Auditory, visual, and somatosensory evoked potentials were recorded twice a week, during the daily 6-h field-off period. E- and B-field exposure had no effect on the early or mid-latency evoked potential components, suggesting that exposure at these levels has no effect on peripheral or central sensory afferent pathways. However, there was a statistically significant decrease in the amplitudes of late components of the somatosensory evoked potential during the 10kV/m and 0.3 G, and 30 kV/m and 0.9 G exposure levels. This result is possibly related to the opiate antagonist effect of electromagnetic field exposure reported by others.

Animals

Operant conditioning of primate triceps surae H-reflex produces reflex asymmetry.

Monkeys are able to increase or decrease triceps surae H-reflex when reward depends on reflex amplitude. Operantly conditioned change occurs over weeks and produces persistent alterations in the lumbosacral spinal cord which should be technically accessible substrates of primate memory. Previous work monitored and conditioned triceps surae H-reflex in one leg. To determine whether H-reflex conditioning in one leg affects the control leg, the present study monitored H-reflexes in both legs while the reflex in one leg underwent HR increases or HR decreases conditioning. Under the HR increases mode, H-reflex increase was much greater in the HR increases leg than in the control leg. Under the HR decreases mode, H-reflex decrease was confined to the HR decreases leg. By showing that conditioning of one leg's H-reflex produces H-reflex asymmetry, the data further define the phenomenon and indicate that the other leg can serve as an internal control for physiologic and anatomic studies exploring the sites and mechanisms of the spinal cord memory substrates.

Animals

Diurnal rhythms in primate spinal reflexes and accompanying cortical somatosensory evoked potentials.

We recorded spinal reflexes and cortical somatosensory evoked potentials (SEPs), elicited by stretching the biceps or the triceps muscle or by electrically stimulating the posterior tibial nerve, from monkeys throughout the day. Amplitudes of the spinal stretch reflex (SSR) and of its electrically evoked analogue, the H-reflex, varied diurnally: both were greatest midway through the lights-off period and smallest during the lights-on period. Stretch-evoked and electrically evoked SEP amplitudes also varied diurnally, but were out of phase with the spinal reflex rhythms. The H-reflex is elicited by direct stimulation of the nerve and thus, unlike the SSR, bypasses the muscle spindle. The H-reflex diurnal rhythm and the phase difference between the spinal reflex and SEP diurnal rhythms indicate that these rhythms are mediated at least in part by central mechanisms. Furthermore, both the spinal reflex and SEP diurnal rhythms appeared to be entrained by the light-dark cycle, which suggests that they may be coupled to the same oscillator. Besides their theoretical importance, these rhythms have important implications for experimental and clinical studies of spinal reflexes and SEPs. These rhythms are especially pertinent to the interpretation of long-term monitoring studies, as are often carried out in the Intensive Care Unit and during lengthy neurosurgical procedures.

Animals

Memory traces in primate spinal cord produced by operant conditioning of H-reflex.

1. Study of memory traces in higher animals requires experimental models possessing well-localized and technically accessible memory traces--plasticity responsible for behavioral change, not dependent on control from elsewhere, and open to detailed investigation. Our purpose has been to develop such a model based on the wholly spinal, largely monosynaptic path of the spinal stretch reflex. Previous studies described operant conditioning of this reflex and of its electrical analog, the H-reflex. In this study, we sought to determine whether conditioning causes changes in the spinal cord that affect the reflex and are not dependent on continued supraspinal influence, and thus qualify as memory traces. 2. Sixteen monkeys underwent chronic conditioning of the triceps surae H-reflex. Eight were rewarded for increasing H-reflex amplitude (HR increases mode), and eight were rewarded for decreasing it (HR decreases mode). In each animal, the other leg was an internal control. Over several months of conditioning, H-reflex amplitude in the conditioned leg rose in HR increases animals and fell in HR decreases animals. H-reflex amplitude in the control leg changed little. 3. After HR increases or HR decreases conditioning, each animal was deeply anesthetized and surgically prepared. The reflex response to supramaximal dorsal root stimulation was measured from the triceps surae nerve as percent of response to supramaximal ventral root stimulation, which was the maximum possible response. Data from both legs were collected before and for up to 3 days after thoracic (T9-10) cord transection. The animal remained deeply anesthetized throughout and was killed by overdose. 4. The reflex asymmetries produced by conditioning were still present several days after transection removed supraspinal influence: reflexes of HR increases animals were significantly larger in HR increases legs than in control legs and reflexes of HR decreases animals were significantly smaller in HR decreases legs than in control legs. 5. Reflex amplitude was much greater in the control legs of anesthetized HR decreases animals than in the control legs of anesthetized HR increases animals. 6. Chronic conditioning had at least two effects on the spinal cord. The first effect, task-appropriate reflex asymmetry, was evident both in the awake behaving animal and in the anesthetized transected animal. The second effect, larger control leg reflexes in HR decreases than in HR increases animals, was evident only in the anesthetized animal. By removing supraspinal control, anesthesia and transection revealed a previously hidden effect of conditioning.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

Retrograde transport of the lectin Phaseolus vulgaris leucoagglutinin (PHA-L) by rat spinal motoneurons.

The lectin Phaseolus vulgaris leucoagglutinin (PHA-L) has been used primarily as an anterograde transport tracer in the CNS. We present evidence of PHA-L retrograde transport by rat spinal motoneurons after injection into the triceps brachii. Labelled motoneurons were localized in specific and well-defined neuron pools in the ventral horn. Primary afferent labelling was not seen in the spinal gray matter. Dorsal rhizotomy did not eliminate or decrease motoneuron labelling. The retrograde transport rate was about 8 mm/day. PHA-L can clearly undergo retrograde, as well as anterograde, transport.

Animals

Spinal stretch reflex and cortical evoked potential amplitudes versus muscle stretch amplitude in the monkey arm.

While investigating operant conditioning of the primate spinal stretch reflex (SSR), we studied SSR amplitude and cortical somatosensory evoked potential (SEP) amplitude as stretch amplitude changed in the monkey arm. Initial muscle length and background EMG activity remained constant. With change in stretch amplitude (and proportional change in stretch velocity and acceleration), changes in SSR and SEP amplitudes were respectively 0.75 and 0.66 as great. The lesser change in SSR amplitude may reflect saturation of Ia afferents, while that in SEP amplitude may also reflect participation of other peripheral receptors.

Animals

Operant conditioning of primate spinal reflexes: effect on cortical SEPs.

Previous studies have demonstrated operant conditioning of the primate spinal stretch reflex (SSR) and of its electrical analog, the H-reflex. We studied the evoked potential recorded over primary somatosensory cortex (SEP) which accompanies the H-reflex to determine whether the initial cortical response changes in the course of conditioned H-reflex change. When H-reflex amplitude changed, SEP amplitude also changed, but only half as much as the H-reflex. The results indicate that, while operant conditioning of the H-reflex has its largest effect on the spinal pathway of the reflex, it also has some effect on supraspinal pathways of the initial cortical response.

Animals

Jendrassik maneuver facilitates soleus H-reflex without change in average soleus motoneuron pool membrane potential.

Facilitation of spinal reflex amplitude by remote muscle contraction, otherwise known as the Jendrassik maneuver (JM), was first shown over 100 years ago, yet the mechanism by which this facilitation operates remains undetermined. Earlier work has eliminated participation of the muscle spindle in JM-induced spinal reflex facilitation, leaving changes in postsynaptic (e.g., change in average soleus motoneuron membrane potential) and presynaptic (e.g., inhibition of presynaptic inhibition) mechanisms as viable candidates. We recorded background EMG in the soleus muscle during JM-induced soleus H-reflex facilitation in humans. The JM in this experiment consisted of wrist muscle contraction. Soleus background EMG was maintained by the subject at either a zero level (e.g., relaxed) or a specified moderate level prior to and during the JM. The JM increased H-reflex amplitude by comparable amounts in both situations, but had no effect on soleus background EMG. Given the well-known relationship between the average motoneuron pool membrane potential and background EMG, we conclude that JM facilitation of the soleus H-reflex is not caused by an increase in background excitatory input to the soleus motoneuron pool. Remaining candidates for mediation of JM induced H-reflex facilitation include change in stimulus-evoked afferent input at some point proximal to the muscle spindle, such as reduction in presynaptic inhibition, or a change in motoneuron input resistance.

Adult