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M C Bushnell

Publications and source records attributed to M C Bushnell.

52 records · Page 3Linked to original sources

Task-related responses of monkey medullary dorsal horn neurons.

Medullary dorsal horn neurons with trigeminal sensory properties have been previously shown to have additional responses associated with cues relevant to the successful execution of a behavioral task. These "task-related" responses were evoked by environmental cues but were independent of the specific stimulus parameters. We have examined further the characteristics of task-related responses in medullary dorsal horn neurons of three monkeys. Single-unit activity was recorded while the monkeys were performing behavioral tasks that required them to discriminate thermal or visual stimuli for a liquid reward. Forty-five percent (34/75) of the medullary dorsal horn neurons studied exhibited task-related activity that was significantly correlated with the stereotypical behavioral events that occurred during the tasks. Similar events occurring outside of the task produced no response. In addition to the task-related activity of these medullary dorsal horn neurons, responses to mechanical and/or thermal stimuli presented within the neuron's receptive field were demonstrated in 28 of 34 cases. These sensory responses also were evoked by the same stimuli presented outside of the behavioral task. Fifteen of the neurons with task-related responses could be activated antidromically from thalamic stimulating electrodes. Task-related responses were categorized according to their relationship to the three phases of the behavioral trial: trial initiation, trial continuation, and trial termination. Although an individual task-related response was associated with a single behavioral event, most medullary dorsal horn neurons (30/34) exhibited a reproducible pattern of task-related responses that occurred during more than one phase of the trial. Trial-initiation task-related responses were subdivided depending on their correlation with specific events that occurred within that phase of the trial. One-third of the 18 excitatory trial-initiation responses were associated with the visual stimulus that cued the monkey to begin the trial; the remaining two-thirds were associated with the monkey's press of the button that actually initiated the trial. Trial-continuation task-related responses (observed while the monkey waited for a thermal stimulus that triggered a rewarded motor response) were shown to be independent of the actual temperature of the thermal stimulus. In addition these trial-continuation task-related responses were also noted during trials without a thermal stimulus, in which the trigger cue was the onset of a light (in a visual task).(ABSTRACT TRUNCATED AT 400 WORDS)

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Wide-dynamic-range dorsal horn neurons participate in the encoding process by which monkeys perceive the intensity of noxious heat stimuli.

The role of dorsal horn wide-dynamic-range (WDR) and nociceptive-specific (NS) neurons in the encoding of the perceived intensity of noxious stimuli was determined while monkeys detected near-threshold changes in the intensity of noxious heat stimuli. Behavioral detection latencies were a reliable measure of the perceived intensity of these stimuli. There was a significant correlation between behavioral detection latency and neuronal discharge of WDR, but not NS neurons. In addition, WDR neurons exhibited greater activity on correctly detected vs non-detected trials, whereas NS neurons did not. We conclude that WDR neurons are involved in the encoding process by which monkeys perceive the intensity of noxious heat stimuli near detection threshold.

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Dorsal horn opiate administration attenuates the perceived intensity of noxious heat stimulation in behaving monkey.

In monkeys trained to detect and discriminate noxious heat stimuli, morphine microinjected into the medullary dorsal horn attenuated the perceived intensity of noxious heat in a dose- and stimulus-dependent fashion. These data demonstrate a pharmacologically specific effect of opiates on the sensory intensity component of pain at the earliest central relay pathway transmitting noxious information.

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The effect of attentive fixation on eye movements evoked by electrical stimulation of the frontal eye fields.

Electrical stimulation of the frontal eye fields of the rhesus monkey evokes saccadic eye movements. Both the amplitude of electrically elicited saccades and the threshold current for eliciting them are primarily determined by the location of the stimulating electrode within the frontal eye fields; however, threshold and amplitude also are systematically affected by the monkey's behavioral state when the stimulation is applied. If the monkey is alert, but not performing a task, saccade amplitudes are largest and thresholds are lowest. Conversely, if the monkey actively fixates a visual target, elicited saccades are smaller and threshold currents are higher. Saccades evoked during fixation have slower velocities appropriate for their reduced amplitude. Phase plane plots of eye velocity versus eye position indicate that these saccades are originally programmed to be smaller and slower, and hence are not large saccades voluntarily braked in mid-flight. As opposed to their amplitude and threshold, the direction of electrically evoked saccades is unaffected by the state of fixation. The state of attentive fixation, but not the visual fixation target itself, is the responsible factor for these effects. These results suggest that there is a difference between the state of active fixation and the state of having the eye still in the orbit without active fixation. The oculomotor system in the latter case is relatively more susceptible to signals from the cerebral cortex.

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The modulation of sensory transmission through the medullary dorsal horn during cortically driven mastication.

During mastication, reflexes are modulated and sensory transmission is altered in interneurons and ascending pathways of the rostral trigeminal sensory complex. The current experiment examines the modulation of sensory transmission through the most caudal part of the trigeminal sensory system, the medullary dorsal horn, during fictive mastication produced by cortical stimulation. Extracellular single unit activity was recorded from the medullary dorsal horn, and multiple unit activity was recorded from the trigeminal motor nucleus in anesthetized, paralyzed rabbits. The masticatory area of sensorimotor cortex was stimulated to produce rhythmic activity in the trigeminal motor nucleus (fictive mastication). Activity in the dorsal horn was compared in the presence and absence of cortical stimulation. Fifty-two percent of neurons classified as low threshold and 83% of neurons receiving noxious inputs were influenced by cortical stimulation. The cortical effects were mainly inhibitory, but 21% of wide dynamic range and 6% of low threshold cells were excited by cortical stimulation. The modulation produced by cortical stimulation, whether inhibitory or excitatory, was not phasically related to the masticatory cycle. It is likely that, when masticatory movements are commanded by the sensorimotor cortex, the program includes tonic changes in sensory transmission through the medullary dorsal horn.

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The medullary dorsal horn: a target for the expression of opiate effects on the perceived intensity of noxious heat.

We examined the effects of morphine microinjected into the medullary dorsal horn (MDH) on the ability of monkeys to detect temperature increases in the noxious heat range. Behavioral detection latency and the percentage of correct detections were used as measures of the perceived intensity of noxious heat stimuli. Three monkeys were trained to detect a change (T2) of 0.4, 0.6, or 1.0 degrees C from a previous noxious heat level of 46 degrees C (T1). Effects on attentional, motivational, and motoric aspects of the monkeys' behavior were assessed by having them detect innocuous cooling and visual stimuli in tasks of similar difficulty. Morphine (1, 3, and 10 micrograms) microinjected into the MDH produced a dose-dependent and stimulus-intensity-dependent increase in the latency to detection of the T2 stimuli. These effects were opiate receptor-mediated since they were antagonized by systemically administered naloxone (0.5 mg/kg, i.m.) given 40 min after the microinjection of morphine. There were no effects of morphine on the behavioral detection latencies to the innocuous cooling and visual stimuli, indicating that the effects of morphine were modality-specific and independent of changes in motivation, attention, or motoric ability. These data demonstrate a pharmacologically specific effect of opiates on the perceived intensity of noxious heat stimuli at the earliest central relay pathway transmitting noxious information.

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Primate frontal eye fields. II. Physiological and anatomical correlates of electrically evoked eye movements.

We studied single neurons in the frontal eye fields of awake macaque monkeys and compared their activity with the saccadic eye movements elicited by microstimulation at the sites of these neurons. Saccades could be elicited from electrical stimulation in the cortical gray matter of the frontal eye fields with currents as small as 10 microA. Low thresholds for eliciting saccades were found at the sites of cells with presaccadic activity. Presaccadic neurons classified as visuomovement or movement were most associated with low (less than 50 microA) thresholds. High thresholds (greater than 100 microA) or no elicited saccades were associated with other classes of frontal eye field neurons, including neurons responding only after saccades and presaccadic neurons, classified as purely visual. Throughout the frontal eye fields, the optimal saccade for eliciting presaccadic neural activity at a given recording site predicted both the direction and amplitude of the saccades that were evoked by microstimulation at that site. In contrast, the movement fields of postsaccadic cells were usually different from the saccades evoked by stimulation at the sites of such cells. We defined the low-threshold frontal eye fields as cortex yielding saccades with stimulation currents less than or equal to 50 microA. It lies along the posterior portion of the arcuate sulcus and is largely contained in the anterior bank of that sulcus. It is smaller than Brodmann's area 8 but corresponds with the union of Walker's cytoarchitectonic areas 8A and 45. Saccade amplitude was topographically organized across the frontal eye fields. Amplitudes of elicited saccades ranged from less than 1 degree to greater than 30 degrees. Smaller saccades were evoked from the ventrolateral portion, and larger saccades were evoked from the dorsomedial portion. Within the arcuate sulcus, evoked saccades were usually larger near the lip and smaller near the fundus. Saccade direction had no global organization across the frontal eye fields; however, saccade direction changed in systematic progressions with small advances of the microelectrode, and all contralateral saccadic directions were often represented in a single electrode penetration down the bank of the arcuate sulcus. Furthermore, the direction of change in these progressions periodically reversed, allowing particular saccade directions to be multiply represented in nearby regions of cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

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Attentional influences on noxious and innocuous cutaneous heat detection in humans and monkeys.

This study examines whether selective attention can influence sensory-discriminative aspects of nociception in humans and monkeys trained to detect innocuous and noxious thermal stimuli. Human subjects had two contact thermodes positioned bilaterally above the upper lip. Upon trial initiation both thermodes heated to either 39 degrees C, an innocuous warm temperature, or 45 degrees C, a slightly noxious temperature. After 4 to 9 sec, the temperature of one thermode increased an additional step of less than 1 degree C. Subjects released a button when they detected this second temperature increase (T2). Three types of trials were presented in order to assess the effects of spatially selective attention on thermal detection. On 40% of the trials a light correctly signaled the location of the thermode on which T2 would occur. On 10% of trials a light incorrectly signaled the location of T2. No signal was presented on the remaining trials. From the 45 degrees C base line, detection latencies were shortest in the correct signal condition, longest in the incorrect signal condition, and intermediate in the unsignaled condition. The percent of undetected T2s was greatest in the incorrect signal condition and least in the correct signal condition. From the 39 degree C base line, the detection latency in the incorrect signal condition was greater than in the unsignaled condition, but the latter latency was not different from the correct signal latency. In addition, the percent of undetected T2s was the same on all three types of trials.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Activity of trigeminothalamic neurons in medullary dorsal horn of awake monkeys trained in a thermal discrimination task.

We analyzed the activity of 51 trigeminothalamic neurons in the medullary dorsal horn (trigeminal nucleus caudalis) of monkeys during the performance of behavioral tasks requiring the monkeys to discriminate innocuous and noxious thermal stimuli applied to the face and to detect the onset of visual stimuli. Static properties of trigeminothalamic neurons in behaving monkeys were similar to those in anesthetized monkeys. Responses to passively presented mechanical and thermal stimuli, receptive-field properties, and conduction velocities did not differ in the awake and anesthetized states. For most wide dynamic range and nociceptive-specific trigeminothalamic neurons, there was a negative correlation between the magnitude of thermally evoked activity and behavioral latencies to discriminate 47 and 49 degrees C stimuli. Thus, both groups of neurons provide information that could be used by the monkey to discriminate noxious thermal stimuli. The magnitude of thermal responses of trigeminothalamic neurons was modulated by the behavioral significance of the stimulus. Behaviorally relevant thermal stimuli presented during the thermal discrimination task produced a greater neuronal response than equivalent irrelevant thermal stimuli presented between behavioral trials or presented while the monkey performed the visual detection task. Neurons whose activity is modulated by behavioral state are likely to be involved in discrimination of thermal stimuli, since the activity of these neurons correlates with the behavioral response to the stimuli and information from the modulated neurons is sent to the thalamus. Some trigeminothalamic neurons that exhibited somatosensory responses also responded to behaviorally relevant stimuli and events associated with trial initiation and receipt of reward in the behavioral tasks. Similar events outside a behavioral task evoked no neuronal responses. These task-related responses were similar to those described previously for medullary dorsal horn neurons not identified as to projection sites (14).(ABSTRACT TRUNCATED AT 400 WORDS)

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Discrimination of innocuous and noxious thermal stimuli applied to the face in human and monkey.

Four humans and one monkey performed two-choice discriminations between simultaneous 3-sec heat stimuli applied to the face. All subjects produced more accurate discriminations in the noxious thermal range (approximately 47 degrees C) than in the innocuous thermal range (approximately 39 degrees C). The difference threshold, defined as the smallest temperature difference detected on 75% of the trials, was smaller for every subject at 47 degrees C than at 39 degrees C. The monkey's discriminative performance was comparable to that of humans in the noxious range, but inferior to that of humans in the innocuous range. Subjects' superior discrimination at noxious temperatures cannot be easily accounted for by differences in primary afferent activity of warm fibers and heat-nociceptive fibers. However, differences in central processing or attentional modulation could contribute to superior discrimination in the noxious range. These findings indicate that heat-sensitive nociceptors are capable of transmitting precise information about noxious thermal input to the skin.

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Primary afferent and sacral dorsal horn neuron responses to vaginal probing in the cat.

An analysis was made of primary afferent and dorsal horn neuron responses to stimulation of genitalia of female cats. Three types of primary afferents responded to vaginal probing. The most common type responded maximally to the on- and off-ramps of non-noxious pressure applied directly to the clitoris. A second type responded similar but to surrounding labia mucosa. The third type showed a tonic discharge during deep vaginal-cervical probing. None of the primary afferents that responded to vaginal probing exhibited after-responses to any stimulus. However, a majority (76%) of wide dynamic range dorsal horn neurons showed increased rates of firing that outlasted the duration of vaginal probing by at least 28 sec. No other type of dorsal horn neuron responded in this manner. It appears that after-responses of wide dynamic range neurons to vaginal stimulation cannot be attributed to after-responses of primary afferents or to supraspinal mechanisms but are produced by mechanisms within the spinal cord.

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An investigation of peak shift and behavioral contrast for autoshaped and operant behavior.

Instrumental treadle press and nonreinforced key peck responses were monitored during discrimination training and generalization testing in pigeons on positive and negative reinforcement schedules. In Experiment 1, six pigeons pressed a treadle for food on a multiple variable-interval extinction schedule. In Experiment 2, three pigeons pressed a treadle to avoid shock on a multiple free-operant avoidance extinction schedule. Different color keylights signaled S+ and S- components. Some positive behavioral contrast occurred during discrimination training, but the effect was small. Pecking occurred to the S+ keylight in Experiment 1 but not in Experiment 2. On stimulus generalization tests, all subjects displayed a positive peak shift when pressing the treadle for food or to avoid shock. However, peak shift was not found for nonreinforced "autopecks" on the stimulus key, although an area shift was observed in Experiment 1. This is the first demonstration of peak shift for pigeons pressing treadles and the only reliable demonstration of peak shift when negative reinforcement maintained responding. These results, in combination with previous demonstrations of peak shift for rats pressing levers and pigeons pecking keys, indicate that peak shift is a general by-product of operant discrimination learning, since it occurs across a variety of the organisms, responses, and reinforcers.

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The effect of reinforcement differences on choice and response distribution during stimulus compounding.

In Experiments I and II, rats were trained to respond on one lever during light and another during tone. The absence of tone and light controlled response cessation. In the multiple schedule of Experiment I, all reinforcements were received for responding in tone or light; in the chain schedule of Experiment II, all reinforcements were received in no tone + no light for not responding. Experiment I subjects, for which tone and light were associated with response and reinforcement increase, responded significantly more to tone-plus-light than to tone or light alone (additive summation). Experiment II subjects, for which tone and light were associated with response increase and reinforcement decrease, responded comparably to tone, light, and tone + light. Thus, additive summation was observed when stimulus-response and stimulus-reinforcer associations in tone and light were both positive, but not when they were conflicting. All subjects in both experiments responded predominantly on the light-correlated lever during tone + light, even when light intensity was reduced in testing. Furthermore, when a light was presented to a subject engaged in tone-associated responding, all subjects immediately switched the locus of responding to the light-correlated lever. No change in locus occurred when a tone was presented to a subject engaged in light-associated responding, irrespective of the stimulus-reinforcer association conditioned to tone. The light-lever preference in tone + light indicates that the heightened responding observed in Experiment I was not the summation of tone-associated behavior with light-associated behavior. Rather, it appears to be the result of a facilitation of one operant (light-associated responding) by the reinforcement-associated cue for the other.

Journal Article↗

A thalamic nucleus specific for pain and temperature sensation.

The existence of a posterolateral thalamic relay nucleus for pain and temperature sensation was postulated in 1911, on the basis of the stroke-induced analgesia and thermanaesthesia found paradoxically in patients with thalamic pain syndrome. Pain or temperature sensations can be evoked in humans by electrical stimulation in a vaguely defined region of the posterolateral thalamus. Here we use anterograde tracing and single unit recordings to demonstrate that there is a distinct nucleus in the posterior thalamus of the macaque monkey that receives a dense, topographic input from spinothalamic lamina I neurons and in which almost all neurons are nociceptive- or thermoreceptive-specific. Immunohistochemical staining showed that this nucleus is defined by a dense calbindin-positive fibre plexus in the macaque, so we applied the same staining method to sections of human thalamus. We found a nearly identical fibre plexus localized within a distinct nucleus that is cytoarchitectonically homologous to the lamina I relay nucleus in the macaque thalamus. The stereotaxic coordinates of this nucleus and its location relative to the main somatosensory representation fit clinical descriptions of the pain-producing region in humans. We conclude that this is a specific thalamic nucleus for pain and temperature sensation in both monkey and human.

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