Identifying auditory cortex encoding abnormalities in schizophrenia: The utility of low‐frequency versus 40 Hz steady‐state measures

Magnetoencephalography (MEG) and EEG have identified poststimulus low frequency and 40 Hz steady‐state auditory encoding abnormalities in schizophrenia (SZ). Negative findings have also appeared. To identify factors contributing to these inconsistencies, healthy control (HC) and SZ group differences were examined in MEG and EEG source space and EEG sensor space, with better group differentiation hypothesized for source than sensor measures given greater predictive utility for source measures. Fifty‐five HC and 41 chronic SZ were presented 500 Hz sinusoidal stimuli modulated at 40 Hz during simultaneous whole‐head MEG and EEG. MEG and EEG source models using left and right superior temporal gyrus (STG) dipoles estimated trial‐to‐trial phase similarity and percent change from prestimulus baseline. Group differences in poststimulus low‐frequency activity and 40 Hz steady‐state response were evaluated. Several EEG sensor analysis strategies were also examined. Poststimulus low‐frequency group differences were observed across all methods. Given an age‐related decrease in left STG 40 Hz steady‐state activity in HC (HC > SZ), 40 Hz steady‐state group differences were evident only in younger participants' source measures. Findings thus indicated that optimal data collection and analysis methods depend on the auditory encoding measure of interest. In addition, whereas results indicated that HC and SZ auditory encoding low‐frequency group differences are generally comparable across modality and analysis strategy (and thus not dependent on obtaining construct‐valid measures of left and right auditory cortex activity), 40 Hz steady‐state group‐difference findings are much more dependent on analysis strategy, with 40 Hz steady‐state source‐space findings providing the best group differentiation.     

Electrophysiological evidence for altered early cerebral somatosensory signal processing in schizophrenia

Various studies have indicated an impairment of sensory signal processing in schizophrenic patients. Anatomical and functional imaging studies have indicated morphological and metabolic abnormalities in the thalamus in schizophrenia. Other results give evidence for an additional role of cortical dysfunction in sensory processing in schizophrenia. Advanced analysis of human median nerve somatosensory evoked potentials (SEPs) reveals a brief oscillatory burst of low-amplitude and high-frequency activity ( approximately 600 Hz), the so-called high frequency oscillations (HFOs). The present study explores the behavior of HFOs in a cohort of schizophrenic patients in comparison to a group of controls. HFOs in the group of patients appeared with a delayed latency. In the low-frequency part of the SEPs an increase in amplitude was found. These results are interpreted to reflect a lack of somatosensory inhibition in the somatosensory pathway, either at a thalamic or a cortical level.     

Overlapping clusters of gray matter deficits in paranoid schizophrenia and psychotic bipolar mania with family history

The purpose of this study was to assess volumetric abnormalities of gray matter throughout the entire brain in patients with paranoid schizophrenia or with bipolar mania compared with control groups. We obtained weighted 3D T1 magnetic resonance images from 23 patients with paranoid schizophrenia, 24 patients with psychotic bipolar mania, and 36 healthy controls. Gray matter volume differences were assessed using optimized volumetric voxel-based morphometry (VBM). Both paranoid schizophrenia and bipolar mania group showed reduction of gray matter volume in the superior temporal gyrus (STG) (Brodmann Area, BA 22 areas), and the inferior parietal lobule, and enlargement of putamen, although different sides of the inferior parietal lobule and putamen were affected in the groups. Our findings showed the presence of overlapping clusters of gray matter deficits in paranoid-type schizophrenia and psychotic bipolar mania. The overlap in gray matter pathology between the two disorders may be attributed to risk factors common to both disorders.     

How much does phase resetting contribute to event-related EEG abnormalities in schizophrenia?

Objective: Patients suffering from schizophrenia demonstrate impaired low frequency electrophysiological responses to stimuli, but it remains unclear whether these abnormalities arise from phase resetting of ongoing oscillations, new phase-locked (evoked) activity or non-phase-locked (induced) activity. Our goal is to clarify the contribution of each of these three processes to the impairment of neural activity during information processing in schizophrenia, by using statistics that do not confound increases in the mean post-stimulus signal with phase resetting. Methods: Thirty-four male schizophrenia patients and 34 healthy matched controls performed an auditory oddball task. We applied the analysis procedure developed by Martinez-Montes et al. [18] based on complex-valued wavelet transform to event-related signal elicited by target stimuli. Results: The largest abnormalities were found for phase-locked delta (1–4 Hz) and non-phase-locked theta (4–8 Hz). Delta phase resetting was moderately impaired and related to symptoms of disorganization. It also predicted evoked theta signal. Conclusion: The substantial reduction of both evoked and induced oscillatory activity in schizophrenia indicates diminished recruitment of brain circuits engaged not only in stimulus-locked perceptual processing but also in more extensive processing less tightly time locked to the stimulus. Although reduced phase resetting makes a lesser contribution, it indicates a deficit in the ability to harness ongoing electrical activity.     

Varying the degree of single-whisker stimulation differentially affects phases of intrinsic signals in rat barrel cortex

Using intrinsic signal optical imaging (ISI), we have shown previously that the point spread of evoked activity in the rat barrel cortex in response to single-whisker stimulation encompasses a surprisingly large area. Given that our typical stimulation consists of five deflections at 5 Hz, the large area of evoked activity might have resulted from repetitive stimulation. Thus in the present study, we use ISI through the thinned skull to determine whether decreasing the degree of single-whisker stimulation decreases the area of the cortical point spread. We additionally outline a protocol to quantify stimulus-related differences in the temporal characteristics of intrinsic signals at a fine spatial scale. In 10 adult rats, whisker C2 was stimulated randomly with either one or five deflections delivered in a rostral-to-caudal fashion. Each deflection consisted of a 0.5-mm displacement of the whisker as measured at the point of contact, 15 mm from the snout. The number of whisker deflections did not affect the area or peak magnitude of the cortical point spread based on the intrinsic signal activity occurring from 0.5 up to 1.5 s poststimulus onset. In contrast, the magnitude and time course of intrinsic signal activity collected after 1.5-s poststimulus onset did reflect the difference in the degree of stimulation. Thus decreasing the degree of stimulation differentially affected the early and late phases of the evoked intrinsic signal response. The implications of the present results are discussed in respect to probable differences in the signal source underlying the early versus later phases of evoked intrinsic signals.     

Single-sweep analysis of the theta frequency band during an auditory oddball task

The P300 component and the oscillatory 4–7 Hz electroencephalographic activity of auditory event-related brain potentials (ERPs) were assessed to study differences between passive and oddball task conditions. Theta responses from 15 adults were analyzed for single-sweep amplitude, phase locking, and enhancement against prestimulus activity. ERPs were characterized by enhanced and strongly phase-locked theta oscillations in the early (0–300 ms) poststimulus epoch, with only the late (300–600 ms) theta responses at Fz and Pz affected by the oddball condition. P300 was strongly associated not only with the concurrent theta oscillations but also with the evoked theta activity preceding P300 (0–300 ms). It was concluded that single theta response parameters can reveal specific functional differences between passive and oddball conditions and that a strong relationship exists between the theta frequency component and the time domain P300 ERP component.     

The best of both worlds: phase-reset of human EEG alpha activity and additive power contribute to ERP generation.

Some authors have proposed that event-related potentials (ERPs) are generated by a neuronal response which is additive to and independent of ongoing activity, others demonstrated that they are generated by partial phase-resetting of ongoing activity. We investigated the relationship between event-related oscillatory activity in the alpha band and prestimulus levels of ongoing alpha activity on ERPs. EEG was recorded from 23 participants performing a visual discrimination task. Individuals were assigned to one of three groups according to the amount of prestimulus total alpha activity, and distinct differences of the event-related EEG dynamics between groups were observed. While all groups exhibited an event-related increase in phase-locked (evoked) alpha activity, only individuals with sustained prestimulus alpha activity showed alpha-blocking, that is, a considerable decrease of poststimulus non-phase-locked alpha activity. In contrast, individuals without observable prestimulus total alpha activity showed a concurrent increase of phase-locked and non-phase-locked alpha activity after stimulation. Data from this group seems to be in favor of an additive event-related neuronal response without alpha-blocking. However, the dissociable EEG dynamics of total and evoked alpha activities together with a complementary simulation analysis indicated a partial event-related reorganization of ongoing brain activity. We conclude that both partial phase-resetting and partial additive power contribute dynamically to the generation of ERPs. The prestimulus brain state exerts a prominent influence on event-related brain responses.     

Synchronization of neuronal activity in the human primary motor cortex by transcranial magnetic stimulation: an EEG study

Using multichannel electroencephalography (EEG), we investigated temporal dynamics of the cortical response to transcranial magnetic stimulation (TMS). TMS was applied over the left primary motor cortex (M1) of healthy volunteers, intermixing single suprathreshold pulses with pairs of sub- and suprathreshold pulses and simultaneously recording EEG from 60 scalp electrodes. Averaging of EEG data time locked to the onset of TMS pulses yielded a waveform consisting of a positive peak (30 ms after the pulse P30), followed by two negative peaks [at 45 (N45) and 100 ms]. Peak-to-peak amplitude of the P30-N45 waveform was high, ranging from 12 to 70 microV; in most subjects, the N45 potential could be identified in single EEG traces. Spectral analysis revealed that single-pulse TMS induced a brief period of synchronized activity in the beta range (15-30 Hz) in the vicinity of the stimulation site; again, this oscillatory response was apparent not only in the EEG averages but also in single traces. Both the N45 and the oscillatory response were lower in amplitude in the 12-ms (but not 3-ms) paired-pulse trials, compared with the single-pulse trials. These findings are consistent with the possibility that TMS applied to M1 induces transient synchronization of spontaneous activity of cortical neurons within the 15- to 30-Hz frequency range. As such, they corroborate previous studies of cortical oscillations in the motor cortex and point to the potential of the combined TMS/EEG approach for further investigations of cortical rhythms in the human brain.     

Stimulus intensity affects early sensory processing: sound intensity modulates auditory evoked gamma-band activity in human EEG.

We studied the effect of different sound intensities on the auditory evoked gamma-band response (GBR). Previous studies observed oscillatory gamma activity in the auditory cortex of animals and humans. For the visual modality, it has been demonstrated that the GBR can be modulated by top-down (attention, memory) as well as bottom-up factors (stimulus properties). Therefore, we expected to find a sound intensity modulation for the auditory GBR. 21 healthy participants without hearing deficits were investigated in a forced-choice discrimination task. Sinusoidal tones were presented at three systematically varied sound intensities (30, 45, 60 dB hearing level). The results of the auditory evoked potentials were predominantly consistent with previous studies. Furthermore, we observed an augmentation of the evoked GBR with increasing sound intensity. The analysis indicated that this intensity difference in the GBR amplitude most likely arises from increased phase-locking. The results demonstrate a distinct dependency between sound intensity and gamma-band oscillations. Future experiments that investigate the relationship between auditory evoked GBRs and higher cognitive processes should therefore select stimuli with an adequate sound intensity and control this variable to avoid confounding effects. In addition, it seems that gamma-band activity is more sensitive to exogenous stimulus parameters than evoked potentials.     

Frequency‐specific disruptions of neuronal oscillations reveal aberrant auditory processing in schizophrenia

Individuals with schizophrenia exhibit abnormalities in evoked brain responses in oddball paradigms. These could result from (a) insufficient salience‐related cortical signaling (P300), (b) insufficient suppression of irrelevant aspects of the auditory environment, or (c) excessive neural noise. We tested whether disruption of ongoing auditory steady‐state responses at predetermined frequencies informed which of these issues contribute to auditory stimulus relevance processing abnormalities in schizophrenia. Magnetoencephalography data were collected for 15 schizophrenia and 15 healthy subjects during an auditory oddball paradigm (25% targets; 1‐s interstimulus interval). Auditory stimuli (pure tones: 1 kHz standards, 2 kHz targets) were administered during four continuous background (auditory steady‐state) stimulation conditions: (1) no stimulation, (2) 24 Hz, (3) 40 Hz, and (4) 88 Hz. The modulation of the auditory steady‐state response (aSSR) and the evoked responses to the transient stimuli were quantified and compared across groups. In comparison to healthy participants, the schizophrenia group showed greater disruption of the ongoing aSSR by targets regardless of steady‐state frequency, and reduced amplitude of both M100 and M300 event‐related field components. During the no‐stimulation condition, schizophrenia patients showed accentuation of left hemisphere 40 Hz response to both standard and target stimuli, indicating an effort to enhance local stimulus processing. Together, these findings suggest abnormalities in auditory stimulus relevance processing in schizophrenia patients stem from insufficient amplification of salient stimuli.     

Distinct M50 and M100 auditory gating deficits in schizophrenia

The time course of the schizophrenia auditory gating deficit may provide clues to mechanisms of impaired cognition. Magnetoencephalography was recorded during a standard paired-click paradigm. Using source strength of the M50 and M100 components for each click, calculated from dipole locations identified as underlying each component for the first click, a ratio of the second divided by the first was used to measure gating. Patients showed a left-hemisphere gating deficit in M50 and a bilateral gating deficit in M100. Hypothesizing that an early deficit may affect later processing, hierarchical regression was used to examine variance shared between the components. A left-hemisphere M100 gating deficit was coupled with the left M50 gating deficit. In contrast, a right-hemisphere M100 gating deficit was unrelated to M50 gating in either hemisphere. Investigations of interhemisphere gating relations may clarify group differences in regional connectivity and their role in gating.     

Event-related fMRI of word classification and successful word recognition in subjects at genetically enhanced risk of schizophrenia

BACKGROUND: Verbal declarative memory is a core deficit in schizophrenia patients, seen to a lesser extent in unaffected biological relatives. Neuroimaging studies suggest volumetric differences and aberrant function in prefrontal and temporal regions in schizophrenia patients compared to controls. These deficits are also reflected in the small number of similar investigations in unaffected biological relatives. However, it is unclear the extent to which dysfunction is genetically mediated or a feature of the established illness. METHOD: Event-related blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was used to measure brain activation in 68 biological relatives of schizophrenia patients (of whom 27 experienced transient or isolated psychotic symptoms) and 21 controls during verbal classification and recognition. RESULTS: During word classification, the high-risk group showed a greater response relative to controls in the right inferior frontal gyrus. During correct recognition (relative to correct rejection), the high-risk group showed significantly greater response relative to controls in the right cerebellum. When the high-risk group was split into those with (HR+) and without (HR-) psychotic symptoms, the increased response in the right inferior frontal gyrus was only seen when the HR+ were compared to controls. The greater cerebellar response was seen when both HR groups were compared to controls. CONCLUSIONS: Activation increases in the right inferior frontal gyrus and cerebellum in high-risk subjects compared to controls during a relatively low-load memory task are likely to represent compensation for genetically mediated abnormalities. This is consistent with a leftward shift of the inverted 'U' load-response model of cognitive function in schizophrenia.     

Ionic mechanism underlying recovery of rhythmic activity in adult isolated neurons

Neurons exhibit long-term excitability changes necessary for maintaining proper cell and network activity in response to various inputs and perturbations. For instance, the adult crustacean pyloric network can spontaneously recover rhythmic activity after complete shutdown resulting from permanent removal of neuromodulatory inputs. Dissociated lobster stomatogastric ganglion (STG) neurons have been shown to spontaneously develop oscillatory activity via excitability changes. Rhythmic electrical stimulation can eliminate these oscillatory patterns in some cells. The ionic mechanisms underlying these changes are only partially understood. We used dissociated crab STG neurons to study the ionic mechanisms underlying spontaneous recovery of rhythmic activity and stimulation-induced activity changes. Similar to lobster neurons, rhythmic activity spontaneously develops in crab STG neurons. Rhythmic hyperpolarizing stimulation can eliminate, but more commonly accelerate, the emergence of stable oscillatory activity depending on Ca(2+) influx at hyperpolarized voltages. Our main finding is that upregulation of a Ca(2+) current and downregulation of a high-threshold K(+) current underlies the spontaneous homeostatic development of oscillatory activity. However, because of a nonlinear dependence on stimulus frequency, hyperpolarization-induced oscillations appear to be inconsistent with a homeostatic regulation of activity. We find no difference in the activity patterns or the underlying ionic currents involved between neurons of the fast pyloric and the slow gastric mill networks during the first 10 days in isolation. Dynamic-clamp experiments confirm that these conductance modifications can explain the observed activity changes. We conclude that spontaneous and stimulation-induced excitability changes in STG neurons can both result in intrinsic oscillatory activity via regulation of the same two conductances.     

Interhemispheric transfer time in patients with auditory hallucinations: an auditory event-related potential study

Central auditory processing in schizophrenia patients with a history of auditory hallucinations has been reported to be impaired, and abnormalities of interhemispheric transfer have been implicated in these patients. This study examined interhemispheric functional connectivity between auditory cortical regions, using temporal information obtained from latency measures of the auditory N1 evoked potential. Interhemispheric Transfer Times (IHTTs) were compared across 3 subject groups: schizophrenia patients who had experienced auditory hallucinations, schizophrenia patients without a history of auditory hallucinations, and normal controls. Pure tones and single-syllable words were presented monaurally to each ear, while EEG was recorded continuously. IHTT was calculated for each stimulus type by comparing the latencies of the auditory N1 evoked potential recorded contralaterally and ipsilaterally to the ear of stimulation. The IHTTs for pure tones did not differ between groups. For word stimuli, the IHTT was significantly different across the 3 groups: the IHTT was close to zero in normal controls, was highest in the AH group, and was negative (shorter latencies ipsilaterally) in the nonAH group. Differences in IHTTs may be attributed to transcallosal dysfunction in the AH group, but altered or reversed cerebral lateralization in nonAH participants is also possible.     

P3 and delta band responses in visual oddball paradigm in schizophrenia

Amplitude reduction of the oddball P3 wave is a well-replicated but non-specific finding of schizophrenia. The time-frequency analysis of single-trial ERP data allows to specify in a reliable manner whether the P3 reduction in schizophrenia is due to the decreased P3 response in single trials or due to the inter-trial variability in the timing of the response. Since the delta response most strongly contributes to the P3 amplitude, we focused to the low frequency range of the time-frequency transformed data. EEG was recorded from chronic schizophrenia patients and matched healthy controls during a simple visual oddball task. The wavelet transforms of the averaged ERP and the single trials were computed to investigate the amplitudes of the evoked (phase-locked) and total (phase-locked+non-phase-locked) delta (1-3 Hz) responses, respectively. Evoked delta activity and P3 amplitude to target stimuli were both reduced significantly in patients with schizophrenia, whereas no such difference was obtained for the total delta activity. The significant reduction of the evoked delta response and the absence of such a difference in the total delta response of schizophrenia patients reveals that the delta band response is weakly phase-locked to stimulus in schizophrenia. This result suggests that the reduced P3 amplitudes in the averaged ERPs of schizophrenia patients result from a temporal jitter in the activation of neural circuits engaged in P3 generation.     

Impaired prepulse inhibition and habituation of acoustic startle response in Japanese patients with schizophrenia

Prepulse inhibition (PPI) and habituation of the acoustic startle reflex (ASR) are considered to be candidate endophenotypes of schizophrenia. However, to our knowledge, only one group has investigated these startle measures in Asian patients with schizophrenia. In the present study, we evaluated these startle measures in 51 Japanese patients with schizophrenia and compared them with those of 55 healthy age- and sex-matched Japanese controls. A human startle response monitoring system was used to deliver acoustic startle stimuli, and record and score the electromyographic activity of the orbicularis oculi muscle. The startle measures examined were mean magnitude of ASR to pulse alone trials in initial block (SR), habituation of ASR during the session (HAB), and PPI at prepulse intensities of 82 dB (PPI82), 86 dB (PPI86), and 90 dB (PPI90) sound pressure level. SR was not significantly different between the patients and controls. Patients displayed significantly reduced HAB and PPI for all prepulse intensities compared to controls. The greatest statistical difference in PPI between patients and controls was found with PPI86. This did not correlate with any clinical variable in each group. Our results indicate that PPI and habituation of ASR are impaired in Asian patients with schizophrenia.     

The amplitude and phase precision of 40 Hz auditory steady-state response depend on the level of arousal

The aim of this study was to investigate, in healthy subjects, the modulation of amplitude and phase precision of the auditory steady-state response (ASSR) to 40 Hz stimulation in two resting conditions varying in the level of arousal. Previously, ASSR measures have shown to be affected by the level of arousal, but the findings are somewhat controversial. Generally, ASSR is diminished in sleep but it may be increased in drowsiness. Besides, ASSR reduction has been observed in schizophrenia. However, schizophrenic patients are known to have a disturbance of arousal level, what makes it pertinent to know the effects of fluctuations in arousal on passive response to gamma-range stimulation. In nine healthy volunteers trains of 40 Hz click stimuli were applied during two conditions: in the “high arousal” condition subjects were sitting upright silently reading a book of interest; in the “low arousal” condition subjects were sitting in a reclined position with eyes closed and the lights turned off. The 64-channel EEG data was wavelet transformed and the amplitude and phase precision of the wavelet transformed evoked potential were decomposed by the recently proposed multi-subject non-negative multi-way factorization (NMWF) (Morup et al. in J Neurosci Methods 161:361–368, 2007). The estimates of these measures were subjected to statistical analysis. The amplitude and phase precision of the ASSR were significantly larger during the low arousal state compared to the high arousal condition. The modulation of ASSR amplitude and phase precision by differences in the arousal level during recording warrants caution when investigating oscillatory brain activity and interpreting the findings of reduced ASSR in schizophrenia. It also emphasizes the necessity of standardized recording procedures and monitoring the level of arousal during ASSR testing.     

Increased frontal phase-locking of event-related theta oscillations in Alzheimer patients treated with cholinesterase inhibitors.

This is a pilot study describing event-related oscillations in patients with Alzheimer-type dementia (AD). Theta responses of 22 mild probable AD subjects according to NINCDS-ADRDA criteria (11 non-treated, 11 treated by cholinesterase inhibitors), and 20 healthy elderly controls were analyzed by using the conventional visual oddball paradigm. We aimed to compare theta responses of the three groups in a range between 4-7 Hz at the frontal electrodes. At F(3) location, theta responses of healthy subjects were phase locked to stimulation and theta oscillatory responses of non-treated Alzheimer patients showed weaker phase-locking, i.e. average of Z-transformed means of correlation coefficients between single trials was closer to zero. In treated AD patients, phase-locking following target stimulation was two times higher in comparison to the responses of non-treated patients. The results indicate that the phase-locking of theta oscillations at F(3) in the treated patients is as strong as the control subjects. The F(4) theta responses were not statistically significant between the groups. Our findings imply that the theta responses at F(3) location are highly unstable in comparison to F(4) in non-treated mild AD patients and cholinergic agents may modulate event-related theta oscillatory activities in the frontal regions.     

Abnormal left superior temporal gyrus volumes in children and adolescents with bipolar disorder: a magnetic resonance imaging study

Abnormalities in left superior temporal gyrus (STG) have been reported in adult bipolar patients. However, it is not known whether such abnormalities are already present early in the course of this illness. Magnetic resonance imaging (MRI) morphometric analysis of STG was performed in 16 DSM-IV children and adolescents with bipolar disorder (mean age+/-SD 15.5+/-3.4 years) and 21 healthy controls (mean age+/-SD 16.9+/-3.8 years). Subjects underwent a 3D spoiled gradient recalled acquisition MRI examination. Using analysis of covariance with age, gender and intra-cranial brain volume as covariates, we found significantly smaller left total STG volumes in bipolar patients (12.5+/-1.5 cm(3)) compared with healthy controls (13.6+/-2.5 cm(3)) (F=4.45, d.f.=1, 32, P=0.04). This difference was accounted for by significantly smaller left and right STG white matter volumes in bipolar patients. Decreased white matter connections may be the core of abnormalities in STG, which is an important region for speech, language and communication, and could possibly underlie neurocognitive deficits present in bipolar patients.     

Forward masking of auditory nerve fiber responses.

1. Responses of single fibers were obtained from the auditory nerve of chinchillas. Tone-burst stimuli consisted of a masking stimulus followed by a probe stimulus. Forward masking of a fiber's response is defined as a reduction in the magnitude of the probe-evoked response caused by the addition of the masking stimulus. 2. The recovery of probe response magnitude as a function of the time interval between masker offset and probe onset (delta T) follows an exponential time course. A relationship between the time course or magnitude of poststimulus recovery and the characteristic frequency (CF) of a fiber was not detected. 3. The iso-forward masking contour near the threshold of the masking effect across masker frequencies approximates a fiber's frequency threshold curve (FTC). In other words, forward masking tuning curves are essentially the same as frequency threshold curves. 4. The frequency dependence of forward masking is compared to that of two-tone suppression. Tonal stimuli outside the boundaries of a fiber's FTC that produce two-tone suppression are ineffective forward maskers. Certain frequency/intensity combinations within the FTC may produce both suppression and forward masking and tones within the remaining area of the FTC produce no suppression but are effective forward maskers. 5. Both the time course and the magnitude of the forward masking effect are dependent on the discharge rate evoked by the masker regardless of the masker's absolute level or spectral content. An increase in masker-evoked excitation causes an increase in time constant and a greater reduction in probe response magnitude, rd. The function relating rd to masker level parallels the firing rate/masker level function up to 40 dB above response threshold. 6. A decrease in masker duration from 100 ms leads to a decrease in both rd and the time constant of recovery. There is no significant difference between the 100 and 200 ms duration conditions. 7. Forward masking in single fibers is related to the period of poststimulus recovery of spontaneous activity, a component of a fiber's response pattern to the masker, and this component is tentatively identified as a period of recovery from short-term adaptation.