Cerebral cortical respiratory-related evoked potentials elicited by inspiratory occlusion in lambs.

Respiratory-related evoked potentials (RREP) elicited by inspiratory mechanical loads have been recorded in humans. Early RREP peaks were hypothesized to be generated by activation of neurons in the somatosensory cortex. An animal model was developed to test this hypothesis in chronically instrumented, awake, spontaneously breathing lambs. Electrocorticogram (ECoG) was recorded bilaterally with ball electrodes on the dural surface over the somatosensory region. Inspiratory occlusions were presented through a face mask or endotracheal tube as interruptions of inspiration. Occlusion-elicited evoked potentials were obtained by computer-signal averaging the ECoG activity. A short-latency positive peak was observed bilaterally in the averaged occlusion-elicited evoked potentials in all animals breathing with the facemask and 5 of 8 lambs with the endotracheal tube. Postmortem identification of the electrode location demonstrated that the ECoG was recorded in the caudal-lateral portion of the somatosensory cortex. These results demonstrate that inspiratory occlusion elicits an evoked potential in the somatosensory cortical region of awake, spontaneously breathing lambs. The lamb cortical RREP is similar to human RREP.     

Detection threshold for inspiratory resistive loads and respiratory-related evoked potentials.

The relationship between detection threshold of inspiratory resistive loads and the peaks of the respiratory-related evoked potential (RREP) is unknown. It was hypothesized that the short-latency and long-latency peaks of the RREP would only be elicited by inspiratory loads that exceeded the detection threshold. The detection threshold for inspiratory resistive loads was measured in healthy subjects with inspiratory-interruption or onset load presentations. In a separate protocol, the RREPs were recorded with resistive loads that spanned the detection threshold. The loads were presented in stimulus attend and ignore sessions. Onset and interruption load presentations had the same resistive load detection threshold. The P(1), N(f), and N(1) peaks of the RREP were observed with loads that exceeded the detection threshold in both attend and ignore conditions. The P(300) was present with loads that exceeded the detection threshold only in the attend condition. No RREP components were elicited with subthreshold loads. The P(1), N(f), and P(300) amplitudes varied with resistive load magnitude. The results support the hypothesis that there is a resistive load threshold for eliciting the RREPs. The amplitude of the RREP peaks vary as a function of load magnitude. The cognitive P(300) RREP peak is present only for detectable loads and when the subject attends to the stimulus. The absence of the RREP with loads below the detection threshold and the presence of the RREP elicited by suprathreshold loads are consistent with the gating of these neural measures of respiratory mechanosensory information processing.     

Effect of inspiratory muscle strength training on inspiratory motor drive and RREP early peak components.

This study investigated the effect of inspiratory muscle strength training (IMST) on inspiratory motor drive [mouth occlusion pressure at 0.1 s (P(0.1))] and respiratory-related evoked potentials (RREP). It was hypothesized that, if IMST increased inspiratory muscle strength, inspiratory motor drive would decrease. If motor drive were related to the RREP, it was further hypothesized that an IMST-related decrease in drive would change RREP latency and/or amplitude. Twenty-three subjects received IMST at 75% of their maximal inspiratory pressure (Pi(max)) with the use of a pressure threshold valve. IMST consisted of four sets of six breaths daily for 4 wk. P(0.1) and the RREP were recorded before and after IMST. Posttraining, Pi(max) increased significantly by 36.0 +/- 2.7%. P(0.1) decreased significantly by 21.9 +/- 5.2%. The increase in Pi(max) was significantly correlated to the decrease in P(0.1). RREP peaks P(1a), N(f), P(1), and N(1) were identified pre- and post-IMST, and there was no difference in either amplitude or latency for those peaks. These results demonstrate that high-intensity IMST significantly increased Pi(max), decreased P(0.1), but did not change the RREP.     

Respiratory-related cortical potentials evoked by inspiratory occlusion in humans

It has long been recognized that humans can perceive respiratory loads. There have been several studies on the detection and psychophysical quantification of mechanical load perception. This investigation was designed to record cortical sensory neurogenic activity related to inspiratory mechanical loading in humans. Inspiration was periodically occluded in human subjects while the electroencephalographic (EEG) activity in the somatosensory region of the cerebral cortex was recorded. The onset of inspiratory mouth pressure (Pm) was used to initiate signal averaging of the EEG signals. Cortical evoked potentials elicited by inspiratory occlusions were observed when C3 and C alpha were referenced to CZ. This evoked potential was not observed with the control (unoccluded) breaths. There was considerable subject variability in the peak latencies that was related to the differences in the inspiratory drive, as measured by occlusion pressure (P0.1). The results of this study demonstrate that neurogenic activity can be recorded in the somatosensory region of the cortex that is related to inspiratory occlusions. The peak latencies are longer than analogous somatosensory evoked potentials elicited by stimulation of the hand and foot. It is hypothesized that a portion of this latency difference is related to the time required for the subject to generate sufficient inspiratory force to activate the afferents mediating the cortical response.     

Effects of timing of inspiratory occlusion on cerebral evoked potentials in humans

Previous studies from these laboratories have shown that airway occlusion applied from the onset of inspiration or during midinspiration is associated with cerebral evoked potentials in human subjects. The hypothesis tested in the present study was that the more abrupt decrease in mouth pressure produced by midinspiratory occlusion will be associated with evoked potentials that have shorter peak latencies and greater peak amplitudes than those produced by occlusions from the onset of inspiration. The second objective of the present study was to determine whether there is bilateral projection of inputs from the respiratory system to the somatosensory cortex. Random presentation of 64 midinspiratory occlusions and 64 occlusions from the onset of inspiration was performed in eight subjects. The inspirations preceding the occlusions served as control. Evoked potentials were recorded from the scalp with electrode pairs Cz-C3 and Cz-C4. Reaction time to each type of occlusion was measured from the burst in electromyogram activity produced by contraction of the muscles encircling the eye. Each type of inspiratory occlusion was associated with evoked potentials that could be recorded bilaterally. The peak amplitudes of the evoked potentials recorded over the right cerebral hemisphere were significantly greater than those recorded from the left side. The peak amplitude was greater and the peak latency shorter for the evoked potentials produced by the midinspiratory occlusions. The results are consistent with the hypothesis that afferents mediating these potentials are stimulated by added loads to breathing and project bilaterally to the somatosensory cortex in humans.     

Inspiratory neuron activity in the ventrolateral medulla of the dog

The purpose of this study was to describe the distribution and activity pattern of respiratory neurons located in the ventrolateral medulla (VLM) of the dog. Spike activity of 129 respiratory neurons was recorded in 23 ketamine-anesthetized spontaneously breathing dogs. Pontamine blue dye was used to mark the location of each neuron. Most VLM neurons displaying respiratory related spike patterns were located in a column related closely to ambigual and retroambigual nuclei. Both inspiratory and expiratory neurons were present with inspiratory units being grouped more rostrally. The predominant inspiratory neuron firing pattern was "late" inspiratory, although eight "early" types were located. All expiratory firing patterns were the late expiratory variety. Each neuron burst pattern was characterized by determining burst duration (BD), spikes per burst (S/B), peak frequency (PF), time to peak frequency (TPF), rate of rise to peak frequency (PF/TPF), and mean frequency. CO2-induced minute ventilation increases were associated with decreases in BD and TPF and increases in PF, S/B, and PF/TPF. In 11 experiments the relative influences of vagotomy and tracheal occlusion on late inspiratory units were compared. Tracheal occlusion increased late inspiratory BD and S/B but did not alter PF/TPF. Vagotomy increased BD and S/B beyond those obtained by tracheal occlusion and, in some neurons, decreased the PF/TPF. We conclude that the location of respiratory units in the VLM of the dog is similar to that in other species, the discharge pattern of VLM respiratory units is similar to those in cat VLM, and vagotomy and tracheal occlusion affect discharge patterns differently.     

The effect of increased background resistance on the resistive load threshold for eliciting the respiratory-related evoked potential.

The detection threshold (DeltaR(50)) of resistive (R) loads is a function of the total background resistance (R(0)). Increased R(0) increases the DeltaR(50), but the ratio DeltaR(50)/R(0) remains constant. The respiratory-related evoked potential (RREP) is elicited only by R loads greater than the cognitive detection threshold, DeltaR(50). We hypothesized that the RREP Nf, P1, and N1 peaks will be elicited only when the added load DeltaR/R(0) is greater than the normal detection threshold, DeltaR(50)/R(0) = 0.30. We also hypothesized that when the R(0) is increased by adding extrinsic R, the RREP will not be elicited if the DeltaR/R(0) is less than the 0.30 ratio. RREPs were recorded with healthy volunteers (n = 20) respiring through a non-rebreathing valve. Three inspiratory R loads that spanned the DeltaR(50)/R(0) = 0.30 detection threshold were presented in two conditions: 1) no added R(0) (R1 < 0.30, R2 > 0.30, R3 > 0.30); and 2) increased R(0) = 13.3 cmH(2)O.l(-1).s (R1 < 0.30, R2 < 0.30, R3 > 0.30). For the control R(0), P1, Nf, and N1 peaks of the RREP were elicited by both R2 and R3, and not present with R1. The increased R(0) decreased R2/R(0) > 1.5 to R2/R(0) < 0.15. With increased R(0), the R1 and R2 loads did not elicit the RREP, but the Nf, P1, and N1 peaks were present for R3. These results demonstrate that the RREP is present if the DeltaR is above the cognitive detection threshold, and the RREP is absent if the load is below the detection threshold. When the R(0) is increased to make the DeltaR/R(0) less than the detection threshold, the DeltaR no longer elicits the RREP.     

Effects of expiratory loading on respiration in humans

We examined the effects of expiratory resistive loads of 10 and 18 cmH2O.l-1.s in healthy subjects on ventilation and occlusion pressure responses to CO2, respiratory muscle electromyogram, pattern of breathing, and thoracoabdominal movements. In addition, we compared ventilation and occlusion pressure responses to CO2 breathing elicited by breathing through an inspiratory resistive load of 10 cmH2O.l-1.s to those produced by an expiratory load of similar magnitude. Both inspiratory and expiratory loads decreased ventilatory responses to CO2 and increased the tidal volume achieved at any given level of ventilation. Depression of ventilatory responses to Co2 was greater with the larger than with the smaller expiratory load, but the decrease was in proportion to the difference in the severity of the loads. Occlusion pressure responses were increased significantly by the inspiratory resistive load but not by the smaller expiratory load. However, occlusion pressure responses to CO2 were significantly larger with the greater expiratory load than control. Increase in occlusion pressure observed could not be explained by changes in functional residual capacity or chemical drive. The larger expiratory load also produced significant increases in electrical activity measured during both inspiration and expiration. These results suggest that sufficiently severe impediments to breathing, even when they are exclusively expiratory, can enhance inspiratory muscle activity in conscious humans.     

Relationship between magnitude estimation of resistive loads, inspiratory pressures, and the RREP P(1) peak.

This study investigated the relationship among resistive load magnitude (DeltaR), the cortical evoked potential P(1) peak amplitude of the respiratory-related evoked potential (RREP), mouth pressure (Pm), esophageal pressure (Pes), transdiaphragmatic pressure (Pdi), and resistive load magnitude estimation (ME) in human subjects. The RREP, Pdi, Pes, Pm, and ME were recorded in response to three DeltaR values. The RREP was recorded from C(3) and C(4), referenced to the vertex C(Z). The group means of the Pdi, Pm, ME, and RREP P(1) amplitude increased with increases in the DeltaR. A log-log plot of the P(1) amplitudes showed a relationship with ME as did Pes, Pdi, and Pm. There were linear log-log relationships between C(Z)-C(3) P(1) amplitude, C(Z)-C(4) P(1) amplitude, and Pdi to ME. Pdi had a linear log-log relationship with C(Z)-C(3) and C(Z)-C(4). These results support the hypothesis that the estimated magnitude of the respiratory load is related to the P(1) amplitude of the RREP. Pm, Pes, and Pdi are mechanically related and correlated with the P(1) peak amplitude, suggesting that the mechanoreceptors mediating the P(1) peak of the RREP are activated by changes in mechanical forces related to the inspiratory pump.     

Thyroarytenoid muscle activity during loaded and nonloaded breathing in adult humans

Previous fiber-optic studies in humans have demonstrated narrowing of the glottic aperture in expiration during application of expiratory resistive loads. Nine healthy subjects were studied to determine the effect of expiratory resistive loads on the electromyographic activity of the thyroarytenoid (TA) muscle, a vocal cord adductor. Four of the nine subjects also underwent the application of inspiratory resistive loads and voluntary prolongation of either inspiratory (TI) or expiratory (TE) time. TA activity was recorded by intramuscular hooked-wire electrodes. During quiet breathing in all subjects, the TA was phasically active on expiration and often tonically active throughout the respiratory cycle. TA expiratory activity progressively increased with increasing levels of expiratory load. Inspiratory loads resulted in increased TA "inspiratory" activity. Voluntary prolongation of TE to times similar to those reached during loaded breathing induced increases in TA expiratory activity similar to those reached during the loaded state. Voluntary prolongation of TI was associated with an increase in TA inspiratory activity. Similar increases in TI during inspiratory loading or voluntary conditions were associated with comparable increases in TA inspiratory activity in three of the four subjects. In conclusion, increased activation of TA during the application of expiratory resistive loads implies that the reported narrowing of glottic aperture during expiratory loading is an active phenomenon. Changes in activation of the TA with resistive loads appear to be related to changes in respiratory pattern.     

Volitional control of reflex cough

Multiple studies suggest a role for the cerebral cortex in the generation of reflex cough in awake humans. Reflex cough is preceded by detection of an urge to cough; strokes specifically within the cerebral cortex can affect parameters of reflex cough, and reflex cough can be voluntarily suppressed. However, it is not known to what extent healthy, awake humans can volitionally modulate the cough reflex, aside from suppression. The aims of this study were to determine whether conscious humans can volitionally modify their reflexive cough and, if so, to determine what parameters of the cough waveform and corresponding muscle activity can be modified. Twenty adults (18-40 yr, 4 men) volunteered for study participation and gave verbal and written informed consent. Participants were seated and outfitted with a facemask and pneumotacograph, and two surface EMG electrodes were positioned over expiratory muscles. Capsaicin (200 μM) was delivered via dosimeter and one-way (inspiratory) valve attached to a side port between the facemask and pneumotachograph. Cough airflow and surface EMG activity were recorded across tasks including 1) baseline, 2) small cough (cough smaller or softer than normal), 3) long cough (cough longer or louder than normal), and 4) not cough (alternative behavior). All participants coughed in response to 200 μM capsaicin and were able to modify the cough. Variables exhibiting changes include those related to the peak airflow during the expiratory phase. Results demonstrate that it is possible to volitionally modify cough motor output characteristics.     

Effects of expiratory resistive loading on the sensation of dyspnea

To determine whether an increase in expiratory motor output accentuates the sensation of dyspnea (difficulty in breathing), the following experiments were undertaken. Ten normal subjects, in a series of 2-min trials, breathed freely (level I) or maintained a target tidal volume equal to (level II) or twice the control (level III) at a breathing frequency of 15/min (similar to the control frequency) with an inspiratory load, an expiratory load, and without loads under hyperoxic normocapnia. In tests at levels II and III, end-expiratory lung volume was maintained at functional residual capacity. A linear resistance of 25 cmH2O.1(-1).s was used for both inspiratory and expiratory loading; peak mouth pressure (Pm) was measured, and the intensity of dyspnea (psi) was assessed with a visual analog scale. The sensation of dyspnea increased significantly with the magnitude of expiratory Pm during expiratory loading (level II: Pm = 9.4 +/- 1.5 (SE) cmH2O, psi = 1.26 +/- 0.35; level III: Pm = 20.3 +/- 2.8 cmH2O, psi = 2.22 +/- 0.48) and with inspiratory Pm during inspiratory loading (level II: Pm = 9.7 +/- 1.2 cmH2O, psi = 1.35 +/- 0.38; level III: Pm = 23.9 +/- 3.0 cmH2O, psi = 2.69 +/- 0.60). However, at each level of breathing, neither the intensity of dyspnea nor the magnitude of peak Pm during loading was different between inspiratory and expiratory loading. The augmentation of dyspnea during expiratory loading was not explained simply by increases in inspiratory activity. The results indicate that heightened expiratory as well as inspiratory motor output causes comparable increases in the sensation of difficulty in breathing.     

Respiratory-related evoked potentials elicited by inspiratory occlusions in double-lung transplant recipients.

This study investigated the role of lung vagal afferents in the respiratory-related evoked potential (RREP) response to inspiratory occlusions by using double-lung transplant recipients as a lung denervation model. Evoked potential recordings in response to inspiratory occlusions were obtained from 10 double-lung transplant (DLT) recipients with normal lung function and 12 healthy control (Nor) subjects under the attend, ignore, and unoccluded conditions. Results demonstrated that early-latency RREP components (P(1), P(1a), N(f), and N(1)) were not significantly different between the DLT and the Nor groups. The late-latency RREP component (P(3)) was identifiable in all DLT subjects during the attend trial. However, P(3) latency was significantly longer in the DLT group compared with the Nor group. The zero-to-peak amplitude of P(3) was also significantly smaller in the DLT group than that in the Nor group during the attend trial. These results suggest that lung vagal afferents were not essential to elicit RREP responses, but may contribute to the cognitive processing of respiratory stimuli.     

Central inspiratory influence on abdominal expiratory nerve activity

Our purpose was to determine whether the intensity of abdominal expiratory nerve discharge is conditioned by the intensity of the preceding inspiratory phrenic discharge, independent of mechanical and chemical afferent influences. In decerebrate, paralyzed, vagotomized cats with bilateral pneumothoraxes, we recorded phrenic and abdominal (cranial iliohypogastric nerve, L1) nerve activities at hyperoxic normocapnia. We reduced the duration and intensity (i.e., integrated peak height) of phrenic nerve discharge for single cycles by stimulating the cut central end of the superior laryngeal nerve (SLN) during the central inspiratory phase (75 microA, 20-50 Hz, 0.2-ms pulse). Premature termination of inspiration consistently reduced expiratory duration (TE) and abdominal expiratory nerve activity (area of integrated neurogram), but the average reduction in TE was much less than the reduction in abdominal nerve activity (14 vs. 51%). Stimulation of the cut central end of the vagus nerve yielded similar results, as did spontaneous premature terminations of inspiration, which we observed in one cat. SLN stimulation during hyperoxic hypercapnia resulted in more variable responses, and higher stimulation frequencies were usually required to abort inspiration. SLN (or vagal) stimulation during expiration consistently increased abdominal expiratory nerve activity. We speculate that this facilitatory response is gated during inspiration, thereby allowing the inspiratory conditioning effect on the subsequent expiration to be expressed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Multichannel EEG analysis of respiratory evoked-potential components during wakefulness and NREM sleep

Airway occlusion in awake humans producesa somatosensory evoked response called the respiratory-related evokedpotential (RREP). In the present study, 29 channel evoked-potentialrecordings were obtained from seven men who were exposed to 250-msinspiratory airway occlusions during wakefulness, stage 1, stage 2, andslow-wave sleep. The RREP recorded during wakefulness was similar toprevious reports, with the unique observation of an additionalshort-latency positive peak with a mean latency of 25 ms. Short-latencyRREP components were maintained in non-rapid-eye-movement (NREM) sleep. The clearly seen N₁ vertex andlate positive complex components during wakefulness were markedlyattenuated during NREM sleep, and two large negative components(N₃₀₀ andN₅₅₀) dominated the sleep RREP.These findings indicate the maintenance of central nervous systemmonitoring of respiratory afferent information during NREM sleep,presumably to facilitate protective arousal responses topathophysiological respiratory phenomena.

     

Chronic Cerebral Hypoperfusion Induces Transient Reversible Monoaminergic Changes in the Rat Brain

Chronic restriction of cerebral blood flow in hypoperfused Wistar rats has been proposed as a new model of cerebrovascular-type dementia. Using this model, we have investigated central monoaminergic neuronal systems that are closely related to higher brain function. Monoamine and monoamine-metabolite levels were determined, as relative monoaminergic markers, at 1 day and 1,3,6 and 12 weeks after the bilateral occlusion of common carotid arteries. Dopaminergic changes in the frontal cortex and striatum were observed in hypoperfused rats at 1–3 weeks following occlusion. Serotonergic changes were recognized at four brain regions examined (frontal cortex, hippocampus, striatum and thalamus+midbrain). In particular, the immediate enhancement of serotonin turnover in the striatum appeared to influence the reaction to the acute ischemic attack such as vasoconstriction produced by hypoperfusion. Our findings suggest that chronic cerebral hypoperfusion induces transient reversible changes in central monoaminergic neuronal function within three weeks of ligation of carotid arteries. This time interval seems to represent a turning point in the process of chronic cerebral hypoperfusion-induced progressive brain injury.     

Respiratory volume-time relationships during resistive loading in the cat.

The first-breath (neural) effects of graded resistive loads added separately during inspiration and expiration was studied in seven anesthetized cats before and after bilateral vagotomy. Additions of airflow resistance during inspiration reduced the volume inspired (VI) and increased inspiratory duration (TI). The duration of the ensuing unloaded expiration (TE) was unchanged. Vagotomy eliminated the TI modulation with inspiratory loads. Tracheal occlusion at the onset of inspiration yielded TI values similar to the fixed values observed following vagotomy. Resistive loads added during expiration produced similar results. Expired volume (VE) decreased and (TE) increased approaching the values obtained after vagotomy. Unlike the inspiratory resistive loads, loading during expiration results in an upward shift in the functional residual capacity (FRC). The FRC shift produces a time lag between the onset of diaphragmatic (EMG) activity and the initiation of airflow of the next (unloaded) inspiration. These studies suggest separate volume-time relationships for the inspiratory and expiratory phases of the breathing cycle. Both relationships are dependent upon vagally mediated volume feedback.     

Ventilatory response to fatiguing and nonfatiguing resistive loads in awake sheep

To study the changes in ventilation induced by inspiratory flow-resistive (IFR) loads, we applied moderate and severe IFR loads in chronically instrumented and awake sheep. We measured inspired minute ventilation (VI), ventilatory pattern [inspiratory time (TI), expiratory time (TE), respiratory cycle time (TT), tidal volume (VT), mean inspiratory flow (VT/TI), and respiratory duty cycle (TI/TT)], transdiaphragmatic pressure (Pdi), functional residual capacity (FRC), blood gas tensions, and recorded diaphragmatic electromyogram. With both moderate and severe loads, Pdi, TI, and TI/TT increased, TE, TT, VT, VT/TI, and VI decreased, and hypercapnia ensued. FRC did not change significantly with moderate loads but decreased by 30-40% with severe loads. With severe loads, arterial PCO2 (PaCO2) stabilized at approximately 60 Torr within 10-15 min and rose further to levels exceeding 80 Torr when Pdi dropped. This was associated with a lengthening in TE and a decrease in breathing frequency, VI, and TI/TT. We conclude that 1) timing and volume responses to IFR loads are not sufficient to prevent alveolar hypoventilation, 2) with severe loads the considerable increase in Pdi, TI/TT, and PaCO2 may reduce respiratory muscle endurance, and 3) the changes in ventilation associated with neuromuscular fatigue occur after the drop in Pdi. We believe that these ventilatory changes are dictated by the mechanical capability of the respiratory muscles or induced by a decrease in central neural output to these muscles or both.     

Adenylate cyclase activity and motor behavior following cerebral ischemia in the unanesthetized gerbil

Five minutes of bilateral carotid occlusion in unanesthetized gerbils produced substantial changes in spontaneous locomotor activity. Behavior was decreased after 1 hr of reperfusion and was increased at 24 hrs post-ischemia. Adenylate cyclase activity was measured in homogenates of frontal cortex and hippocampus at 90 min and 24 hrs following 5 min of cerebral ischemia. Enzyme activity was determined in the absence and presence of the activators guanosine-5'-triphosphate (GTP), guanylyl-5'-imidodiphosphate (GppNHp), isoproterenol (Iso) plus GTP, and forskolin (Fors) plus GTP. Homogenates responded with expected increases over basal adenylate cyclase activity with addition of all activators. An additional small increase in isoproterenol-stimulated activity was observed in frontal cortex homogenates at 90 min post-ischemia. No other significant changes in adenylate cyclase activity were observed after either 90 min or 24 hrs of reperfusion. The substantial increases in locomotor activity evident at 24 hrs after transient ischemia are not associated with measurable changes in adenylate cyclase activity in homogenates of frontal cortex or hippocampus.     

Effects of Presentation Rate and Attention on Auditory Discrimination: A Comparison of Long-Latency Auditory Evoked Potentials in School-Aged Children and Adults

Decoding human speech requires both perception and integration of brief, successive auditory stimuli that enter the central nervous system as well as the allocation of attention to language-relevant signals. This study assesses the role of attention on processing rapid transient stimuli in adults and children. Cortical responses (EEG/ERPs), specifically mismatch negativity (MMN) responses, to paired tones (standard 100–100Hz; deviant 100–300Hz) separated by a 300, 70 or 10ms silent gap (ISI) were recorded under Ignore and Attend conditions in 21 adults and 23 children (6–11 years old). In adults, an attention-related enhancement was found for all rate conditions and laterality effects (L>R) were observed. In children, 2 auditory discrimination-related peaks were identified from the difference wave (deviant-standard): an early peak (eMMN) at about 100–300ms indexing sensory processing, and a later peak (LDN), at about 400–600ms, thought to reflect reorientation to the deviant stimuli or “second-look” processing. Results revealed differing patterns of activation and attention modulation for the eMMN in children as compared to the MMN in adults: The eMMN had a more frontal topography as compared to adults and attention played a significantly greater role in childrens’ rate processing. The pattern of findings for the LDN was consistent with hypothesized mechanisms related to further processing of complex stimuli. The differences between eMMN and LDN observed here support the premise that separate cognitive processes and mechanisms underlie these ERP peaks. These findings are the first to show that the eMMN and LDN differ under different temporal and attentional conditions, and that a more complete understanding of children’s responses to rapid successive auditory stimulation requires an examination of both peaks.