MEG does not reveal impaired sensory gating in first-episode schizophrenia.

OBJECTIVE: The inability to adequately suppress the second of two identical stimuli is called sensory gating deficit and can be studied by recording evoked potentials to auditory stimuli, e.g. the P50 and the N100. It has been considered the physiological correlate of schizophrenia patients' perception of being flooded by sensory impressions. According to the notion that the gating deficit constitutes a genetic trait, we expected to demonstrate the phenomenon in first-episode schizophrenia patients by using Magnetencephalography (MEG). METHODS: Eighteen inpatients in remission of their first psychotic episode and 24 healthy, age- and sex-matched control subjects participated in the study. Diagnoses, psychopathology, and handedness were assessed with established instruments. Stimulation was performed with the double click paradigm (ISI 500 ms, ITI 9-10 s). MEG recordings of 15 patients and 18 controls entered further analyses with the software BESA for spatio-temporal source analyses and statistical analyses with MATLAB. RESULTS: Neither P50 nor N100 responses differed statistically between the groups, which means that gating was not impaired in this sample of first-episode schizophrenia patients. CONCLUSIONS: These results are not in line with the majority of studies on sensory gating in schizophrenia, however, studies on first-episode patients are scarce. The most likely reasons for not observing a gating deficit in our study are patients' first-episode status and atypical antipsychotic medication.

The effect of temporal context on the sustained pitch response in human auditory cortex.

Recent neuroimaging studies have shown that activity in lateral Heschl's gyrus covaries specifically with the strength of musical pitch. Pitch strength is important for the perceptual distinctiveness of an acoustic event, but in complex auditory scenes, the distinctiveness of an event also depends on its context. In this magnetoencephalography study, we evaluate how temporal context influences the sustained pitch response (SPR) in lateral Heschl's gyrus. In 2 sequences of continuously alternating, periodic target intervals and a more irregular baseline interval, the distinctiveness of the target was decreased in 1 of 2 ways--either by increasing the pitch strength of the baseline or by decreasing the pitch strength of the target. The results show that the amplitude of the SPR increases monotonically with the distinctiveness of the target. Moreover, SPR amplitude is greater for the sequence, where the pitch strength of the target is varied, compared with the condition, where the baseline is varied. Two subsequent experiments show that the amplitude of the SPR increases as duty cycle decreases, in a pitch "strength" contrast and in a pitch "value" contrast. These results indicate that the SPR adapts to recent stimulus history, enhancing the response to rare and brief events.

Structural and functional asymmetry of lateral Heschl's gyrus reflects pitch perception preference.

The relative pitch of harmonic complex sounds, such as instrumental sounds, may be perceived by decoding either the fundamental pitch (f0) or the spectral pitch (fSP) of the stimuli. We classified a large cohort of 420 subjects including symphony orchestra musicians to be either f0 or fSP listeners, depending on the dominant perceptual mode. In a subgroup of 87 subjects, MRI (magnetic resonance imaging) and magnetoencephalography studies demonstrated a strong neural basis for both types of pitch perception irrespective of musical aptitude. Compared with f0 listeners, fSP listeners possessed a pronounced rightward, rather than leftward, asymmetry of gray matter volume and P50m activity within the pitch-sensitive lateral Heschl's gyrus. Our data link relative hemispheric lateralization with perceptual stimulus properties, whereas the absolute size of the Heschl's gyrus depends on musical aptitude.

Neuromagnetic correlates of streaming in human auditory cortex.

The brain is constantly faced with the challenge of organizing acoustic input from multiple sound sources into meaningful auditory objects or perceptual streams. The present study examines the neural bases of auditory stream formation using neuromagnetic and behavioral measures. The stimuli were sequences of alternating pure tones, which can be perceived as either one or two streams. In the first experiment, physical stimulus parameters were varied between values that promoted the perceptual grouping of the tone sequence into one coherent stream and values that promoted its segregation into two streams. In the second experiment, an ambiguous tone sequence produced a bistable percept that switched spontaneously between one- and two-stream percepts. The first experiment demonstrated a strong correlation between listeners' perception and long-latency (>60 ms) activity that likely arises in nonprimary auditory cortex. The second demonstrated a covariation between this activity and listeners' perception in the absence of physical stimulus changes. Overall, the results indicate a tight coupling between auditory cortical activity and streaming perception, suggesting that an explicit representation of auditory streams may be maintained within nonprimary auditory areas.

Recovery and refractoriness of auditory evoked fields after gaps in click trains.

When clicks are presented in a train at a rate above approximately 5 Hz, they evoke a sustained field in human auditory cortex that can be recorded by magnetoencephalography. In this study we evaluated how this sustained field continues when a click train is interrupted by a silent gap. The stimuli were click trains with interclick intervals of either 12 or 24 ms, which produce pitches of 83.3 or 41.7 Hz, respectively. The click trains were 996 ms in duration with a gap of 12, 24, 48, 96, or 192 ms beginning 504 ms post-stimulus onset. The sustained field for click trains with short gaps was similar to the one evoked by a continuous click train. Subtraction of the response evoked by a solitary click train of 504 ms enabled estimation of the sustained field in the interval after the gap. The comparison revealed that the sustained field amplitude after the gap was larger than that at the onset of the initial click train in the interval from 150 to 350 ms after onset, and the difference decreased with gap duration. In contrast, the transient P1m was refractory for gaps up to 48 ms, but had nearly recovered its initial amplitude for gaps of 192 ms. We discuss how these results might relate to the perception, i.e. if an interrupted click train is perceived as one continuous sound with a transient gap or as two successive events.

Middle latency auditory-evoked fields reflect psychoacoustic gap detection thresholds in human listeners.

The resolution of the temporal processing in the primary auditory cortex (PAC) was studied in human listeners by using temporal gaps of 3, 6, 10, and 30 ms inserted in 100-ms noise bursts. Middle latency auditory-evoked fields (MAEFs) were recorded and evaluated by spatio-temporal source analysis. The dependency of the neurophysiological activation at about 37 ms (P37m) on the temporal position of the gap was investigated by inserting silent periods 5, 20, and 50 ms after noise burst onset. The morphology of the waveforms evoked by the gap showed that the MAEFs were largely determined by the on-response to the noise burst following the gap. The comparison of the source waveforms revealed two major effects: 1) the amplitudes of the MAEFs increased with longer gap durations and 2) the amplitudes increased with the length of the leading noise burst. When the gap was inserted after 50 ms, a significant deflection of the collapsed left and right hemisphere data was observed for all gap durations. The P37m amplitude failed to reach significance for the shortest gap duration of 3 ms when the gap occurred after 20 and 5 ms. These neuromagnetically derived minimum detectable gap responses closely resembled psychoacoustic thresholds obtained from the same subjects (leading noise burst, 50 ms: 2.4 ms; 20 ms: 3.2; and 5 ms: 5.3 ms). The correspondence between psychoacoustic thresholds and the cortical activation indicates that the recording of MAEFs provides an objective and noninvasive tool to assess cortical temporal acuity.

Temporal resolution of the human primary auditory cortex in gap detection.

The temporal resolution of the primary auditory cortex was studied by recording the magnetic middle latency fields (MAEF) evoked by gaps of 3, 6 and 9 ms inserted in the middle of 600 ms broadband noise bursts. Spatio-temporal source modelling showed that a significant neural representation as reflected by MAEF responses is present at gap durations as low as 3 sms. The comparison of the MAEF waveforms elicited by the onset, gap and offset of the noise bursts indicates that the gap related response near threshold is largely determined by the onset to the burst following the gap. The electro-physiologically derived minimum detectable gap closely resembled the psychoacoustic threshold of 2.0 ms obtained in the same subjects.

The representation of peripheral neural activity in the middle-latency evoked field of primary auditory cortex in humans(1).

Short sweeps with increasing instantaneous frequency (up-chirps) designed to compensate for the propagation delay along the human cochlea enhance the magnitude of wave V of the auditory brainstem responses, while time reversed sweeps (down-chirps) reduce the magnitude of wave V [Dau, T., Wegner, O., Mellert, V., Kollmeier, B., J. Acoust. Soc. Am. 107 (2000) 1530-1540]. This effect is due to synchronisation of frequency channels along the basilar membrane and it indicates that cochlear phase delays are preserved up to the input of the inferior colliculus. The present magnetoencephalography study was designed to investigate the influence of peripheral synchronisation on the activation in primary auditory cortex. Spatio-temporal source analysis of middle-latency auditory evoked fields (MAEFs) elicited by clicks and up- and down-chirps showed that up-chirps elicited significantly larger MAEF responses compared to clicks or down-chirps. Both N19m-P30m magnitude and its latency are influenced by peripheral cross-channel phase effects. Furthermore, deconvolution of the empirical source waveforms with spike probability functions simulated with a cochlear model indicated that the source waves for all stimulus conditions could be explained with the same unit-response function, i.e. a far field recorded cortical response of a very small cell assembly along the medio-lateral axis of Heschl's gyrus that receives input from a small number of excitatory fibres. The conclusion is that (i) phase delays between channels in the auditory pathway are preserved up to primary auditory cortex, and (ii) MAEFs can be described by a convolution of a unit-response function with the summary neural activity pattern of the auditory nerve.

Morphology of Heschl's gyrus reflects enhanced activation in the auditory cortex of musicians.

Using magnetoencephalography (MEG), we compared the processing of sinusoidal tones in the auditory cortex of 12 non-musicians, 12 professional musicians and 13 amateur musicians. We found neurophysiological and anatomical differences between groups. In professional musicians as compared to non-musicians, the activity evoked in primary auditory cortex 19-30 ms after stimulus onset was 102% larger, and the gray matter volume of the anteromedial portion of Heschl's gyrus was 130% larger. Both quantities were highly correlated with musical aptitude, as measured by psychometric evaluation. These results indicate that both the morphology and neurophysiology of Heschl's gyrus have an essential impact on musical aptitude.

Sustained magnetic fields reveal separate sites for sound level and temporal regularity in human auditory cortex.

Magnetoencephalography was used to investigate the relationship between the sustained magnetic field in auditory cortex and the perception of periodic sounds. The response to regular and irregular click trains was measured at three sound intensities. Two separate sources were isolated adjacent to primary auditory cortex: One, located in lateral Heschl's gyrus, was particularly sensitive to regularity and largely insensitive to sound level. The second, located just posterior to the first in planum temporale, was particularly sensitive to sound level and largely insensitive to regularity. This double dissociation to the same stimuli indicates that the two sources represent separate mechanisms; the first would appear to be involved with pitch perception and the second with loudness. The delay of the offset of the sustained field was found to increase with interclick interval up to 200 ms at least, which suggests that the sustained field offset represents a sophisticated offset-monitoring mechanism rather than simply the cessation of stimulation.

Intracerebral sources of human auditory steady-state responses.

The objective of this study was to localize the intracerebral generators for auditory steady-state responses. The stimulus was a continuous 1000-Hz tone presented to the right or left ear at 70 dBSPL. The tone was sinusoidally amplitude-modulated to a depth of 100% at 12, 39, or 88 Hz. Responses recorded from 47 electrodes on the head were transformed into the frequency domain. Brain electrical source analysis treated the real and imaginary components of the response in the frequency domain as independent samples. The latency of the source activity was estimated from the phase of the source waveform. The main source model contained a midline brainstem generator with two components (one vertical and lateral) and cortical sources in the left and right supratemporal plane, each containing tangential and radial components. At 88 Hz, the largest activity occurred in the brainstem and subsequent cortical activity was minor. At 39 Hz, the initial brainstem component remained and significant activity also occurred in the cortical sources, with the tangential activity being larger than the radial. The 12-Hz responses were small, but suggested combined activation of both brainstem and cortical sources. Estimated latencies decreased for all source waveforms as modulation frequency increased and were shorter for the brainstem compared to cortical sources. These results suggest that the whole auditory nervous system is activated by modulated tones, with the cortex being more sensitive to slower modulation frequencies.