A comparative magnetoencephalographic study of cortical activations evoked by noxious and innocuous somatosensory stimulations

We recorded somatosensory-evoked magnetic fields and potentials produced by painful intra-epidermal stimulation (ES) and non-painful transcutaneous electrical stimulation (TS) applied to the left hand in 12 healthy volunteers to compare cortical responses to noxious and innocuous somatosensory stimulations. Our results revealed that cortical processing following noxious and innocuous stimulations was strikingly similar except that the former was delayed approximately 60 ms relative to the latter, which was well explained by a difference in peripheral conduction velocity mediating noxious (Adelta fiber) and innocuous (Abeta fiber) inputs. The first cortical activity evoked by both ES and TS was in the primary somatosensory cortex (SI) in the hemisphere contralateral to the stimulated side. The following activities were in the bilateral secondary somatosensory cortex (SII), insular cortex, cingulate cortex, anterior medial temporal area and ipsilateral SI. The source locations did not differ between the two stimulus modalities except that the dipole for insular activity following ES was located more anterior to that following TS. Both ES and TS evoked vertex potentials consisting of a negativity followed by a positivity at a latency of 202 and 304 ms, and 134 and 243 ms, respectively. The time course of the vertex potential corresponded to that of the activity of the medial temporal area. Our results suggested that cortical processing was similar between noxious and innocuous stimulation in SI and SII, but different in insular cortex. Our data also implied that activities in the amygdala/hippocampal formation represented common effects of noxious and tactile stimulations.     

Jaw-opening reflex after CO2 laser stimulation of the perioral region in man

CO₂ laser pulses selectively excite A-δ and C mechano-thermal nociceptors in the superficial layers of the skin. To study the jaw-opening reflex elicited by a purely nociceptive input, we delivered laser pulses to the perioral region in 15 subjects. Sensory threshold was very low (9 mJ/mm²). High-intensity noxious laser pulses (more than 4 × sensory threshold) evoked a single phase of electromyogram suppression (laser silent period, LSP) at an onset latency of 70 ms in the contracted masseter and temporal muscles, bilaterally. Even maximum-intensity laser pulses failed to activate the suprahyoid muscles. The recovery curves to paired laser stimuli showed that at short interstimulus intervals the test LSP was strongly suppressed. At about 380 ms it recovered to 50%, i.e. its recovery curve resembled that of the masseter late silent period after electrical mental nerve stimulation (SP2). In experiments studying the interaction with heterotopic stimuli and non-nociceptive responses, chin-taps or electrical shocks delivered to the supraorbital, infraorbital or mental nerves before laser stimulation strongly suppressed the LSP. A preceding perioral laser pulse strongly suppressed the masseter SP evoked by supraorbital stimulation and the SP2 evoked by mental stimulation, but left SP1 unaffected. We conclude that the perioral A-δ fibre input elicits a jaw-opening reflex simply by inhibiting the jaw-closers. The LSP response is mediated by a multisynaptic chain of brainstem interneurons and shares with the masseter SP2 part of the central circuit in the ponto-medullary region. We also propose that a common centre processes the various inputs for jaw opening. Received: 18 July 1997 / Accepted: 20 October 1997     

Cortical responses to noxious stimuli during sleep

We used magnetoencephalography to study effects of sleep on cortical responses to noxious stimuli and to clarify the mechanisms underlying pain perception. For a noxious stimulus, painful intra-epidermal electrical stimulation, which selectively activates A-delta fibers, was applied to the dorsum of the left hand. While awake, subjects were asked to count the number of stimuli silently (Attention) or ignore the stimuli (Control). During sleep, magnetic fields recorded in stage 1 sleep and stage 2 sleep were analyzed. One main component at a latency around 140-160 ms was identified in the awake condition. Multiple source analysis indicated that this main component was generated by activities in the contralateral primary somatosensory cortex (SI), bilateral secondary somatosensory cortex (SII) and insular cortex. The medial temporal area (MT) and cingulate cortex were activated later than the main component. Cortical responses in the contralateral SI, ipsilateral SII and MT, bilateral insula and cingulate cortex were significantly enhanced in Attention as compared with Control. The main component 1 M as well as later magnetic fields were markedly attenuated during sleep, suggesting that all these cortical areas are involved in pain cognition.     

The role of the subthalamic nucleus in the response of globus pallidus neurons to stimulation of the prelimbic and agranular frontal cortices in rats

Summary We investigated how the cerebral cortex can influence the globus pallidus by two routes: the larger, net inhibitory route through the neostriatum and the separate, smaller, net excitatory route through the subthalamic nucleus. Stimulation (0.3 and 0.7 mA) of two regions of frontal agranular (motor) cortex and of the medial orbitofrontal cortex centered in the prelimbic cortex typically elicited one or more of the following extracellularly recorded responses in over 50% of tested cells: an initial excitation (approximately 6 ms latency), a short inhibition (15 ms latency) and a late excitation (29 ms latency). Some other cells responded with an excitatory response only (18 ms latency). The excitatory responses largely arise from the subthalamic route. Kainic acid or electrolytic lesion of the subthalamic nucleus eliminated most excitatory responses and greatly prolonged the duration (16 vs 50 ms) of the inhibition. Subthalamic neurons typically showed one or more of the following responses to cortical stimulation: an early excitatory response (4 ms latency), an inhibitory period (9 ms) and a late excitatory response (16 ms). The early response was seen after motor cortex but not prelimbic stimulation. The timing of the globus pallidus and subthalamic responses suggest the operation of a reciprocal inhibitory/excitatory pathway. Two reciprocal interactions were indicated. First, pallidal inhibition may disinhibit the subthalamus and, via a feedback pathway onto the same pallidal cells, act to terminate the neostriatal-induced inhibition. Second, there may be a feedforward pathway from pallidal cells to subthalamic neurons to a different group of pallidal cells. This pathway could act to suppress competing responses. Thus the subthalamus may have three actions: 1) an early direct cortical and 2,3) later reciprocal feedforward and feedback excitatory antagonism of the neostriatal mediated inhibition of globus pallidus.     

Intracortical circuits in rat anterior cingulate cortex are activated by nociceptive inputs mediated by medial thalamus

We investigated the afferents and intracortical synaptic organization of the anterior cingulate cortex (ACC) during noxious electrical stimulation. Extracellular field potentials were recorded simultaneously from 16 electrodes spanning all layers of the ACC in male Sprague-Dawley rats anesthetized by halothane inhalation. Laminar-specific transmembrane currents were calculated with the current source density analysis method. Two major groups of evoked sink currents were identified: an early group (latency = 54.04 +/- 2.12 ms; 0.63 +/- 0.07 mV/mm(2)) in layers V-VI and a more intense late group (latency = 80.07 +/- 4.85 ms; 2.16 +/- 0.22 mV/mm(2)) in layer II/III and layer V. Multiunit activities were evoked mainly in layer V and deep layer II/III with latencies similar to that of the early and late sink groups. The evoked EPSP latencies of pyramidal neurons in layers II/III and V related closely with the sink currents. The sink currents were inhibited by intracortical injection of CNQX (1 mM, 1 microl), a glutaminergic receptor antagonist, and enhanced by intraperitoneal (5 mg/kg) and intracortical (10 microg/microl, 1 microl) injection of morphine, a mu-opioid receptor agonist. Paired-pulse depression was observed with interpulse intervals of 50 to 1,000 ms. High-frequency stimulation (100 Hz, 11 pulses) enhanced evoked responses in the ACC and evoked medial thalamic (MT) unit activities. MT lesions blocked evoked responses in the ACC. Our results demonstrated that two distinct synaptic circuits in the ACC were activated by noxious stimuli and that the MT is the major thalamic relay that transmits nociceptive information to the ACC.     

Comparison of anterior cingulate and primary somatosensory neuronal responses to noxious laser-heat stimuli in conscious, behaving rats

In this study, we investigated single-unit responses of the primary sensorimotor cortex (SmI) and anterior cingulate cortex (ACC) to noxious stimulation of the tail of the rat. The influences of morphine on these nociceptive responses were also compared. Multiple single-unit activities were recorded from two eight-channel microwire arrays chronically implanted in the tail region of the SmI and ACC, respectively. CO2 laser-heat irradiation of the middle part of the tail at an intensity slightly higher than that causing a maximal tail flick response was used as a specific noxious stimulus. Examined individually, ACC neurons were less responsive than SmI neurons to laser-heat stimulus, in that only 51% of the ACC units (n = 125) responded compared with 88% of the SmI units (n = 74). Among these responsive ACC units, many had a very long latency and long-lasting excitatory type of response that was seldom found in the SmI. When ensemble activities were examined, laser heat evoked both short- (60 approximately 150 ms) and long-latency (151 approximately 600 ms) responses in the SmI and ACC. Latencies of both responses were longer in the ACC. Furthermore, a single dose of 2.5-10 mg/kg morphine intraperitoneally suppressed only the long latency response in the SmI, but significantly attenuated both responses in the ACC. These effects of morphine were completely blocked by prior treatment with the opiate receptor blocker, naloxone. These results provide further evidence suggesting that the SmI and ACC may play different roles in processing noxious information.     

Temporal analysis of the flow from V1 to the extrastriate cortex in humans

We previously examined the cortical processing in response to somatosensory, auditory and noxious stimuli, using magnetoencephalography in humans. Here, we performed a similar analysis of the processing in the human visual cortex for comparative purposes. After flash stimuli applied to the right eye, activations were found in eight cortical areas: the left medial occipital area around the calcarine fissure (primary visual cortex, V1), the left dorsomedial area around the parietooccipital sulcus (DM), the ventral (MOv) and dorsal (MOd) parts of the middle occipital area of bilateral hemispheres, the left temporo-occipito-parietal cortex corresponding to human MT/V5 (hMT), and the ventral surface of the medial occipital area (VO) of the bilateral hemispheres. The mean onset latencies of each cortical activity were (in ms): 27.5 (V1), 31.8 (DM), 32.8 (left MOv), 32.2 (right MOv), 33.4 (left MOd), 32.3 (right MOv), 37.8 (hMT), 46.9 (left VO), and 46.4 (right VO). Therefore the cortico-cortical connection time of visual processing at the early stage was 4-6 ms, which is very similar to the time delay between sequential activations in somatosensory and auditory processing. In addition, the activities in V1, MOd, DM, and hMT showed a similar biphasic waveform with a reversal of polarity after 10 ms, which is a common activation profile of the cortical activity for somatosensory, auditory, and pain-evoked responses. These results suggest similar mechanisms of the serial cortico-cortical processing of sensory information among all sensory areas of the cortex.     

Phasic pupil dilation response to noxious stimulation in normal volunteers: relationship to brain evoked potentials and pain report

Pupillary response to noxious stimulation was investigated in men (n = 11) and women (n = 9). Subjects experienced repeated trials of noxious electrical fingertip stimulation at four intensities, ranging from faint to barely tolerable pain. Measures included pupil dilation response (PDR), pain report (PR), and brain evoked potentials (EPs). The PDR began at 0.33 s and peaked at 1.25 s after the stimulus. Multivariate mixed-effects analyses revealed that (a) the PDR increased significantly in peak amplitude as stimulus intensity increased, (b) EP peaks at 150 and 250 ms differed significantly in both amplitude and latency across stimulus intensity, and (c) PR increased significantly with increasing stimulus intensity. Men demonstrated a significantly greater EP peak amplitude and peak latency at 150 ms than did women. With sex and stimulus intensity effects partialled out, the EP peak latency at 150 ms significantly predicted PR, and EP peak amplitude at 150 ms significantly predicted the PDR peak amplitude.     

Magnetoencephalographic study of the neural responses in body perception

A fundamental trait of human beings is the ability to discern information communicated by others. The human body is one of the important sources of such information. To date, several researchers have reported two body-selective regions in the brain—the extrastriate body area (EBA) and fusiform body area. As compared to the number of studies on spatial distribution, studies on the temporal processing of body perception are few. The electroencephalography (EEG) findings of a recent study indicate that observation of the human body induces a remarkable response leading to the generation of event-related-potentials that peak at 190 ms. However, source localization by using EEG has limitations. The advantage of magnetoencephalography (MEG) is that it enables localization of cortical activities and has excellent temporal resolution. In this study, we used MEG to measure the neural responses underlying the perception of the human body. Our results suggest that cortical activation induced by body images was observed in the bilateral EBA region with a latency of 190 ms and right-hemispheric dominance. Our study revealed the regions involved and the latency differences between these regions in body perception. Further, our results show the usefulness of MEG for body perception studies and suggest that like the face, the body plays a unique role in the human recognition process.     

Simultaneous early processing of sensory input in human primary (SI) and secondary (SII) somatosensory cortices.

Simultaneous early processing of sensory input in human primary (SI) and secondary (SII) somatosensory cortices. The anatomic connectivity of the somatosensory system supports the simultaneous participation of widely separated cortical areas in the early processing of sensory input. We recorded evoked neuromagnetic responses noninvasively from human primary (SI) and secondary (SII) somatosensory cortices to unilateral median nerve stimulation. Brief current pulses were applied repetitively to the median nerve at the wrist at 2 Hz for 800-1,500 trials. A single pulse was omitted from the train at random intervals (15% of omissions). We observed synchronized neuronal population activity in contralateral SII area 20-30 ms after stimulation, coincident in time with the first responses generated in SI. Both contra- and ipsilateral SII areas showed prominent activity at 50-60 ms with an average delay of 13 ms for ipsilateral compared with contralateral responses. The refractory behavior of the early SII responses to the omissions differed from those observed at approximately 100 ms, indicative of distinct neuronal assemblies responding at each latency. These results indicate that SII and/or associated cortices in parietal operculum, often viewed as higher-order processing areas for somatosensory perception, are coactivated with SI during the early processing of intermittent somatosensory input.     

Error processing--evidence from intracerebral ERP recordings

Over the last decade, several authors have described an early negative (Ne) and a later positive (Pe) potential in scalp event-related potentials (ERPs) of incorrect choice reactions. The aim of the present study was to investigate the intracerebral origin and distribution of these potentials. Seven intractable epileptic patients participated in the study. A total of 231 sites in the frontal, temporal, and parietal lobes were investigated by means of depth electrodes. A standard visual oddball paradigm was performed, and electroencephalogram (EEG) epochs with correct and incorrect motor reactions were averaged independently. Prominent, mostly biphasic, ERP complexes resembling scalp Ne/Pe potentials were consistently observed in several cortical locations after incorrect trials. The most consistent findings were obtained from mesiotemporal structures; in addition to P3-like activity found after correct responses, an Ne/Pe complex was generally detected after incorrect trials. The Pe had a longer latency than the P3. Other generators of Ne/Pe-like potentials were located in different regions of the frontal lobe. The latency of the Ne was shortest in parietal, longer in temporal, and longest in frontal regions. Our findings firstly show that multiple cortical structures generate Ne and Pe. In addition to the rostral anterior cingulate cortex, the mesiotemporal and some prefrontal cortical sites seem to represent integral components of the brain's error-checking system. Secondly, the coupling of Ne and Pe to a complex suggests a common origin of Ne and Pe. Thirdly, the latency differences of the Ne across lobes suggest that the Ne is primarily elicited in posterior and temporal, and only later in frontal regions.     

Electrophysiological Explorations of the Cause and Effect of Inhibition of Return in a Cue–Target Paradigm

Facilitation and inhibition of return (IOR) are, respectively, faster and slower responses to a peripherally cued target. In a spatially uninformative peripheral cueing task, facilitation is normally observed when the interval between the cue and target stimulus, the stimulus onset asynchrony (SOA), is shorter than 250 ms, while IOR is normally observed when an SOA greater than 250 ms is used. Since Posner and Cohen’s (Attention and performance X, 1984) seminal study, IOR has become an actively investigated component of orienting. In this study, using ERPs and the source localization algorithm, LORETA, we seek to examine the brain mechanisms involved in IOR by localizing the different stages of processing after the appearance of a cue that captures attention exogenously. Unlike previous ERP investigations of IOR, this study analyzes the neural activity (via EEG) produced in response to the cue, prior to the appearance of the target. Neural activations were approximately divided into three stages. In the early stage (110–240 ms), involved activations are in the prefrontal cortex, the bilateral intraparietal cortex, and the contralateral occipito-temporal cortex. In the middle stage (240–350 ms), activations are primarily found in the frontal cortex and the parietal cortex. In the late stage (350–650 ms), the main activations are in the occipito-parietal cortex, but unlike in the early stage, the activation areas have shifted to the hemisphere ipsilateral to the cued location. These findings indicate that IOR is related to both attentional and motor response processes and suggest that the time course of initial facilitation and IOR is concurrent and mediated by two neural networks. Building upon our results, electrophysiological, electroencephalographic, and behavioral results in the literature and extending previous spatial theories of IOR, we propose here a spatio-temporal theory of IOR based upon post-cue dynamics.     

Fibroblast growth factor-1 improves the survival and regeneration of rat vagal preganglionic neurones following axon injury

Self-initiated leg movement in standing humans is preceded by a medio-lateral preparatory balance adjustment (PBA); however, such preparatory balance control is often absent in reflex-like stepping responses evoked by whole-body instability. The presence or absence of the PBA may reflect a task-dependent modulation of the response serving to preserve lateral stability (PBA present) or avoid delay in the lifting of the foot (PBA absent). To examine whether such task-dependent modulation can occur during more stereotypical limb movements, we examined spinally-mediated withdrawal responses evoked by noxious stimulation of the foot. Results showed that rapid limb withdrawal was preceded by a large PBA when subjects were standing but not when they were supine. The PBA caused limb withdrawal to the noxious stimulation to be delayed. However, the onset of the PBA in the standing trials was equivalent in timing to the onset latency of the classic withdrawal responses recorded during the supine trials. Evidence of a preparatory balance adjustment evoked, in advance of a delayed withdrawal response, at very rapid latencies (underlying muscle activation at 70-120 ms) may raise new questions about the neural mechanisms underlying the co-ordination of balance and movement.     

Nociceptive neurons in area 24 of rabbit cingulate cortex.

1. Single-unit responses in area 24 of cingulate cortex were examined in halothane-anesthetized rabbits during stimulation of the skin with transcutaneous electrical (TCES, 3-10 mA), mechanical (smooth or serrated forceps to the dorsal body surface or graded pressures of 100-1,500 g to the stabilized ear) and thermal (> 25 degrees C) stimulation. 2. Of 542 units tested in cingulate cortex, 150 responded to noxious TCES (> or = 6 mA), 93 of 221 units tested responded to noxious mechanical (serrated forceps) and 9 of 47 units tested responded to noxious heat (> 43 degrees C) stimuli. Twenty-five percent of the units that responded to noxious mechanical stimuli also responded to noxious heat stimuli. The only innocuous stimulus that evoked activity in cingulate cortex was a "tap" to the skin and this was effective for 11 of 14 tested units. 3. In 74 units that produced excitatory responses to TCES of the contralateral ear, response latency was 166 +/- 11.3 (SE) ms and response duration was 519 +/- 52.1 ms. 4. Twenty of the 150 units that responded to noxious TCES were initially inhibited. These responses were usually < 1 s in duration (17 of 20 units), whereas responses in the other 3 lasted for over 20 s. 5. Most units had broad receptive fields, because noxious mechanical stimuli anywhere on the dorsal surface of the rabbits, including the face and ears, evoked responses. A small number of units for which the entire body surface was tested (3 of 15 units) had receptive fields limited to the ears, rostral back, and forepaws. 6. Fifteen of 33 units tested had no preferential responses to noxious TCES of the ipsilateral and contralateral ears. Of the remaining units, 10 had a greater response to contralateral and 8 had a greater response to ipsilateral stimuli. 7. The locations of 186 units were histologically verified. Most nociceptive cingulate units were in dorsal area 24b in layers III (n = 35), II (n = 13), or V (n = 9). 8. Cortical knifecut lesions were made in five rabbits to determine if the responses in area 24 were dependent on lateral or posterior cortical inputs. These lesions did not alter the percentage of units driven by noxious stimuli nor response latency. 9. Injections of lidocaine were made into medial parts of the thalamus in six animals and injection and recording sites analyzed histologically.(ABSTRACT TRUNCATED AT 400 WORDS)     

Altered responses of human elbow flexors to peripheral-nerve and cortical stimulation during a sustained maximal voluntary contraction

 The short-latency electromyographic response evoked by transcranial magnetic stimulation (MEP) increases in size during fatigue, but the mechanisms are unclear. Because large changes occur in the muscle action potential, we tested whether changes in the response to stimulation of the peripheral motor nerve could fully account for the increase in the MEP. Subjects (n=8) performed sustained maximal voluntary contractions (MVCs) of the right elbow flexors for 2 min. During the contraction, the MEP and the response to supramaximal stimulation of motor-nerve fibres in the brachial plexus were alternately recorded. During the contraction, responses to motor-nerve stimulation increased in area by 87±35% (mean±SD) in the biceps brachii and 74±30% in the brachioradialis, but the area of the MEPs increased by 153±86% and 175±122%, respectively. Thus, the increase in the MEP was greater than the increase in the peripheral M-wave. The onset latency of the MEP in the biceps brachii increased by 0.7±0.6 ms (range: –0.2 to 1.9 ms) during the sustained contraction. A smaller increase occurred in response to peripheral nerve stimulation (0.3±0.3 ms; from –0.3 to 0.9 ms). In the contralateral elbow flexors, neither responses to transcranial magnetic stimulation nor responses to motor-nerve stimulation changed in size or latency. During the sustained contraction, the short silent period after stimulation of the peripheral nerve (48±5 ms in biceps brachii and 48±4 ms in brachioradialis) increased in duration by about 12 ms (to 61±12 ms and 60±9 ms, respectively), whereas the silent period following transcranial magnetic stimulation increased from 238±39 ms in biceps brachii and 243±34 ms in brachioradialis to 325±41 ms and 343±42 ms, respectively. During a sustained MVC, while the motor responses to peripheral and to cortical stimulation grow concurrently, growth of the MEP cannot be entirely accounted for by changes in the muscle action potential. Hence, some of the increase in MEP size during fatigue must reflect changes in the central nervous system. Increased latency of the MEPs and lengthening of the peripherally evoked silent period are consistent with decreased excitability of the alpha motoneurone pool. Thus, an increased response from the motor cortex to the magnetic stimulus remains a likely contributor to the increase in the size of the MEP in fatigue. Received: 11 September 1998 / Accepted: 28 January 1999     

Nociceptive responsiveness during slow-wave sleep and waking in the rat

Brainstem neurons that are thought to modulate pain are reported to have state-dependent discharge rates. Yet, the effect of behavioral state upon nociceptive transmission has not been well studied. Therefore, we examined responses to noxious thermal stimulation of the rat hindpaw presented during different behavioral states. Noxious thermal stimuli were applied to rats as they spontaneously cycled through waking and sleeping states. Two different methods of heating the paw - a focused light bulb ("radiant heat") and a CO2 laser ("laser heat")-were employed. Regardless of the heating method used, rats withdrew from noxious thermal stimulation when it was applied in each behavioral state tested. When rats were tested with radiant heat, the withdrawal latency from noxious heat was shorter during slow-wave sleep than during waking. In contrast, when tested with laser heat, there was no difference in either the response latency or magnitude evoked by noxious heat across sleep/wake states. Despite the fact that rats withdrew from noxious heat (using either method of application) applied during sleep, the rats quickly returned to sleep afterwards. The latency to sleep after noxious stimulation was significantly greater during waking than during sleeping. The behavioral response to noxious thermal stimulation includes both an initial motor withdrawal which is enhanced during sleep and arousal or alerting which is suppressed during sleep. Therefore, pain evokes at least two distinct reactions that are differentially modulated across sleep/wake cycles.     

Do non-dopaminergic neurons in the ventral tegmental area play a role in the responses elicited in A10 dopaminergic neurons by electrical stimulation of the prefrontal cortex?

It is rapidly becoming apparent that the prefrontal cortex (PFC) plays a major role in controlling the activity of midbrain dopaminergic (DA) neurons. We have previously demonstrated that electrical stimulation of the PFC elicits inhibition-excitation (IE) and excitation (E) activity patterns in DA neurons in the ventral tegmental area (VTA; A10 cell group). Since non-DA neurons in the VTA are cortically innervated, synapse upon DA neurons and appear to have an inhibitory impact, we determined the extent to which the responses of these neurons to stimulation of the PFC could account for the responses seen in DA neurons upon cortical stimulation. Stimulation of the PFC (0.25 mA and 1.0 mA) elicited three categories of response in the majority of VTA non-DA neurons. Types I and II were characterised by a short-to-moderate latency excitation (referred to as “early excitations”), in the latter case preceded by inhibition. Type III responses consisted of inhibition in the absence of an early excitation. Elements of these responses were compared with the temporal characteristics of key elements of responses elicited in DA neurons by PFC stimulation. Although the early excitations in non-DA neurons preceded the inhibitions in DA neurons exhibiting IE responses, the early excitations began approximately 100 ms before the inhibitions in DA neurons and often ended several tens of milliseconds before the inhibitions began, making a causal relationship between these events unlikely. The inhibitions in Type III responses, combined with the inhibitions which followed the early excitations in many Type I and II responses, showed temporal characteristics that suggested a possible causal relationship with the excitations in DA neurons exhibiting E responses, but not those exhibiting IE responses. However, since the excitatory phases of E and IE responses appear to be homologous, the lack of involvement of non-DA neurons in the excitatory phase of IE responses tends to cast doubt on the involvement of non-DA neurons in the excitation during E responses. In fact, the most coherent impression that emerges is that non-DA neurons in the VTA do not influence the activity of A10 DA neurons on a short time-scale (i.e. phasically), but instead may influence activity on a longer time-scale (i.e. tonically). Received: 3 March 1997 / Accepted: 18 August 1997     

Sensory receptors with unmyelinated (C) fibers innervating the skin of the rabbit's ear

The cutaneous receptive properties of unmyelinated (C) fibers of the rabbit's great auricular nerve were determined by single-unit recordings. The majority of C-fiber units could be excited by cutaneous stimulation, and such sensory units fell into three major categories on the basis of responses to mechanical and thermal stimulation of their cutaneous receptive fields: low-threshold mechanoreceptors, nociceptors, or specific thermoreceptors. The majority of afferent elements were nociceptive, and all nociceptors responded to strong mechanical stimulation. Three types of nociceptors could be distinguished by their responses to thermal stimuli. Polymodal nociceptors responded to heat with thresholds of 40-55 degrees C and typically displayed enhanced responses or sensitization after noxious heating of their receptive fields. High-threshold mechanoreceptors failed to respond promptly to heat before noxious cutaneous stimulation which, however, elicited subsequent back-ground activity or sensitivity to heat. A third type of nociceptor responded to cold but not to heat. Low-threshold mechanoreceptors were identified by their brisk responses to very gentle, slowly moving mechanical stimulation of their receptive fields, and were readily distinguished from any element classified as nociceptive by their lower mechanical thresholds. Rapid innocuous warming or cooling excited some of the low-threshold mechanoreceptors. Specific thermoreceptors, both warming and cooling types, were rare, insensitive to mechanical stimulation, and responded to very slight changes in temperature. In contrast to the sensitization to heat, which was characteristic of most nociceptors, specific warming receptors displayed depressed thermal responses after noxious heating of their receptive fields. These results provide further evidence of the similarity of C-fiber receptors innervating hairy skin of different species. Some differences from past reports and additional features are described.     

Event-related perturbations in an electrophysiological measure of auditory sensitivity: effects of probability, intensity and repeated sessions

It is often held that novel or salient stimuli are followed by a brief period of orienting or alerting during which sensory processes are facilitated. Evidence for such a period of facilitation was sought in a paradigm in which evoked responses to weak auditory probe stimuli were examined when given in the presence of salient foreground stimuli, which were varied in probability and intensity, and which were given in two replicate sessions. The background probe stimuli consisted of a continuous train of auditory pip stimuli delivered at a rate of 40 pips per second. Under such conditions of repetitive stimulation a steady-state rhythm (SSR), which is believed to reflect summated early and middle latency evoked responses, is established in the EEG at a corresponding frequency of 40 Hz. The 40 Hz SSR was extracted using a digital averaging and filtering technique and examined continuously for changes in amplitude and latency. The rhythm showed a brief episode during which the latencies of response were decreased. The reduction in latency was greatest at 186 ms after the foreground stimulus, at which time the latencies of individual peaks in the rhythm were reduced by about 3.5 ms. The magnitude of the latency reduction response was larger for intense and for rare stimuli, and showed long-term decrement during the second session. Event-related potential and heart rate responses to the foreground stimulus were also affected by probability, intensity and session, but not in the same pattern. It was hypothesized that the latency shift in the 40 Hz SSR reflects a brief period of sensitization during alerting or orienting responses.