The MMN is a derivative of the auditory N100 response.

We argue that the mismatch negativity (MMN), elicited by rare auditory events, is generated by the same neural mechanisms as the N100, elicited by any audible stimulus. To date, the MMN has been considered to be a unique index of auditory sensory memory and a component which is functionally and spatially separate from the N100 response because: (i) MMN and N100 appear to have different generator locations; (ii) the MMN occurs too late to be an N100; (iii) the MMN, as opposed to the N100, is elicited by stimulus omissions. By utilizing neural modeling and EEG/MEG results, we show that the above reasoning relies on unwarranted assumptions and propose that the MMN is, essentially, an amplitude- and latency-modulated N100 response. This study offers a physiologically constrained and theoretically plausible framework whereby brain dynamics in terms of stimulus feature maps and their reorganization may be used to describe various memory- and learning-related effects of human auditory cognition.

The auditory n100m response reflects changes in speech fundamental frequency.

We studied the cortical activation underlying perception of variations in speech fundamental frequency (F0) as indexed by the amplitude, latency and source location of the auditory N100m response registered with magnetoencephalography (MEG). Ten subjects were presented with Finnish vowels with either a constant or an ascending/descending F0. We found that the human auditory cortex is sensitive to these time-varying changes in the F0 of speech: vowels with a constant F0 elicited more prominent N100m responses than did vowels with ascending or descending changes in F0. These results suggest that the speech-related behavior of the N100m arises out of cortical sensitivity to variations in the F0 and its harmonics which underlie the perception of pitch and intonation. The present observations are interpreted in terms of the interrelatedness of speech production and perception.

Spectral characterization of ongoing and auditory event-related brain processes.

Brain processes phase-locked to stimuli can be readily observed with electro- and magnetoencephalography (EEG & MEG, respectively) using stimulus-triggered averaging of the measured signal. The detection of non-phase-locked brain processes depends on the method used for analyzing the unaveraged data. Here we introduce a technique, partition-referenced moment (PRM) power spectrum, which uses established spectral estimation algorithms but yields a power spectrum with sharp, easily distinguishable peaks in an otherwise level spectrum even when the signal (such as EEG & MEG) is of the one-over-frequency-slope type. Employing this method and wavelet transforms, we show that transient auditory brain responses are followed by dispersed small-magnitude power reductions. Power reductions occurred around 400-600 ms and were specific to ongoing 10 Hz-oscillations. The PRM-method also indicated ongoing oscillations in the 15-30 Hz frequency range where power reductions occurred at around 200-400 ms. Thus, the presented methods enable the straightforward detection of ongoing brain oscillations and their association with event-related power changes.

Periodic glottal excitation and formant frequencies in the perception of vowels.

Voiced speech is created by the fluctuating vocal folds generating the glottal pulseform. This excitation signal is the source of the speech fundamental frequency and its harmonic integer multiples. Periodic glottal excitation is required for the elicitation of speech-specific cortical processes indexed by the auditory N100m response. Here, we studied the cortical processing underlying the perception of the vowels /a/ and /u/ produced using normal and aperiodic phonation. The behavior of the N100m, registered with magnetoencephalography (MEG), was studied in 10 subjects. The amplitude and latency of the N100m as well as the center of gravity of the activated cortical areas varied as a function of stimulus periodicity. Further, the presence of glottal excitation had differential effects on the latency of the N100m elicited by the vowels /a/ and /u/. Thus, changes affecting the perceptual quality of speech signals without changing their phonetic content modify the dynamics of human auditory cortex.

Behavioral detection of spatial stimuli is reflected in auditory cortical dynamics.

We studied the cortical processing of spatial stimuli by magnetoencephalographic (MEG) measurements using broadband noise bursts presented from eight sound source directions in the horizontal plane. The stimuli were individually created for each subject by using three-dimensional (3D) sound techniques. The subjects carried out a behavioral task where their accuracy for localizing the 3D stimuli was established. We found that the auditory N100m response was sensitive to the sound source direction, exhibiting contralaterally more preponderant responses in both the left and the right hemisphere. Generally, responses were more prominent in the right hemisphere. The behavioral performance of the subjects correlated positively with N100m amplitude organization, showing that the dynamics of auditory cortex predict behavioral sound detection.

Auditory evoked responses are additive to brain oscillations.

The generation mechanism of stimulus-evoked electro- and magnetoencephalographic (EEG & MEG) responses has remained controversial. One view holds that evoked responses are independent components, additive to ongoing brain activity. The other view holds that evoked responses are generated via stimulus-induced phase reorganization of ongoing brain activity. This issue has been commonly addressed with signal processing techniques that assume a high level of stationarity (i.e., unchanging properties over time) of the measured signal. Here we used signal analysis methods suitable for analyzing non-stationary signals. We found that auditory stimulation leads to a large power increase of the poststimulus signal compared to prestimulus level. Linear superposition of the (time-domain) averaged response and the unaveraged prestimulus signal accounted for 90% of the power increase. Further, we found that auditory stimulation does not lead to a phase-coherent state of ongoing oscillations. Taken together our results show that auditory evoked responses are directly additive to ongoing oscillations and only 10% of the observed power increases are explained by non-phase-locked brain activity. When examining evoked brain activity with methods providing simultaneous frequency and time information, emphasizing temporal accuracy is likely to provide more accurate descriptions of non-stationary processes of the human brain.

Auditory scene analysis and sensory memory: the role of the auditory N100m.

We consider the neural dynamics underlying auditory streaming, the perceptual grouping of transient auditory events, by using neural modeling and magnetoencephalographic (MEG) measurements in humans. We demonstrate that spatial variations in the strength of feedback inhibition leads to differential amplitude modulation (AM) tuning resembling that found in animal models. In our model, neurons respond selectively to stimuli presented at different onset-to-onset interstimulus intervals (ISIs), and their summed activity (corresponding to the MEG signal) exhibits both transient and sustained responses (SRs) at fast ISIs. In MEG measurements utilizing 2-s trains of 50-ms stimuli presented at 0-1950 ms ISIs, we observed the transient N100m and SRs predicted by the model, with a prominent SR emerging for discrete stimuli at ISIs below 200 ms. Our results explain why, at fast stimulus rates, the amplitude of the auditory N100m appears to be strongly attenuated even though auditory cortex continues to respond vigorously to the stimuli. The results suggest that the longer and shorter forms of auditory sensory memory may be reflected in the N100m and the SR, respectively. As the emergence of the SR coincides with the stimuli being perceived as auditory streams, our study suggests that auditory sensory memory as indexed by transient and sustained cortical activity might underlie auditory scene analysis.

Cortical activity elicited by isolated vowels and diphthongs.

Cortical activity underlying speech perception has been studied mostly by using isolated vowels with constant formant frequencies. Speech, however, is characterized by formant transitions whereby formant frequencies change as a function of time. We used magnetoencephalography (MEG) to investigate cortical activity elicited by isolated vowels and diphthongs containing formant transitions. Ten subjects were presented with two isolated vowels /a/ and /u/ and diphthongs /au/ and /ua/. Stimulus duration was 200 ms, and the diphthongs started and ended with a 50-ms constant-formant period and included a 100-ms linear transition period. Apart from studying the auditory N100m response, we examined subsequent brain activity in a 500-ms poststimulus time window, as the transitions were expected to elicit activity also in later stages of cognitive processing. All the stimuli elicited prominent N100m responses. Thereafter, both the isolated vowels and diphthongs elicited sustained brain activity lasting up to 500 ms. The present observations indicate that identification of the speech sounds as well as changes in their identity are reflected in the auditory N100m. Notably, the stimuli appeared to elicit left-hemispheric activity resembling the N400, typically obtained by using more complicated speech stimuli such as words and sentences.

Memory traces for words as revealed by the mismatch negativity.

Brain responses to the same spoken syllable completing a Finnish word or a pseudo-word were studied. Native Finnish-speaking subjects were instructed to ignore the sound stimuli and watch a silent movie while the mismatch negativity (MMN), an automatic index of experience-dependent auditory memory traces, was recorded. The MMN to each syllable was larger when it completed a word than when it completed a pseudo-word. This enhancement, reaching its maximum amplitude at about 150 ms after the word's recognition point, did not occur in foreign subjects who did not know any Finnish. These results provide the first demonstration of the presence of memory traces for individual spoken words in the human brain. Using whole-head magnetoencephalography, the major intracranial source of this word-related MMN was found in the left superior temporal lobe.

Human cortical processing of auditory events over time.

An essential feature of the human brain is the ability to extract information from temporally distributed events in the auditory environment. We addressed this temporal encoding ability by modelling how stimulus rate is represented in the auditory cortex. We propose that a cortical representation of stimulus rate can be achieved through the oscillatory properties of nerve cells. Using non-invasive brain measures, we tested the prediction of the model that multiple rebound responses (RRs) occur after the ending of stimulation. MEG recordings revealed successive RRs which originated in the same areas as the N1s elicited by the auditory stimuli at latencies predicted by the model. Our modelling and experimental results therefore provide evidence that the temporal structure of the auditory environment is decomposed in human auditory cortex by cells performing bandpass filtering on periodic input.

Magnetoencephalographic (MEG) localization of the auditory N400m: effects of stimulus duration.

The effects of stimulus duration on the elicitation and equivalent current dipole (ECD) localization of the auditory N400(m) were studied in two subject groups, either familiar or unfamiliar with Finnish language, using a sentence-processing paradigm with incongruent ending words of either short or long duration. Long-duration words elicited a broad response at around 400 ms, the generator location(s) of which could not be reliably determined using ECD estimation. In contrast, short-duration words elicited a sharp, strong-amplitude response at about 400 ms latency and it's source location could be reliably determined as being in the vicinity of auditory cortex. Subjects unfamiliar with the Finnish language elicited no response at the 400 ms range. Thus, the use of short-duration words appears to be an important prerequisite for the elicitation and localization of N400m. The differential amplitude behaviour of the N400m between the two subject groups further suggests that comprehension of the semantic content of the speech message is also required.

The periodic structure of vowel sounds is reflected in human electromagnetic brain responses.

Periodicity, which is caused by the vibration of the vocal folds, is an inherent feature of vowel sounds. Whether this periodic structure is reflected in cerebral processing of vowels was addressed via the use of non-invasive brain research methods combined with advanced stimulus production methodology. We removed the contribution of the source of the periodic structure, the glottal excitation produced by the vocal folds, from vowel stimuli and found that electromagnetic responses generated in the auditory cortex reflect this removal. The N1(m) amplitude decreased even though the rest of the acoustical features of the stimuli were identical. Thus, we conclude that speech production mechanisms have significant effects on human brain dynamics as reflected by magnetoencephalography and electroencephalograph.

Suppression of transient 40-Hz auditory response by haloperidol suggests modulation of human selective attention by dopamine D2 receptors.

Cognitive processes including selective attention may depend on synchronous activity of neurons at the gamma-band (around 40Hz). To determine the effect of neuroleptic challenge on transient auditory evoked 40-Hz response, simultaneous measurement of 122-channel magnetoencephalogram (MEG) and 64-channel electroencephalogram (EEG) was used. Either 2mg of dopamine D(2)-receptor antagonist haloperidol or a placebo was administered orally to 11healthy subjects in a double-blind randomized crossover design in two separate sessions. The subjects attended to tones presented to one ear and ignored those presented to the other ear. Haloperidol significantly suppressed the transient 40-Hz electric response to the attended stimuli, while no significant effect was observed in the electric responses to the unattended tones or in the magnetic responses. The present result suggests that dopamine D(2) receptors modulate selective attention.

Sound localization in the human brain: neuromagnetic observations.

Sound location processing in the human auditory cortex was studied with magnetoencephalography (MEG) by producing spatial stimuli using a modern stimulus generation methodology utilizing head-related transfer functions (HRTFs). The stimulus set comprised wideband noise bursts filtered through HRTFs in order to produce natural spatial sounds. Neuromagnetic responses for stimuli representing eight equally spaced sound source directions in the azimuthal plane were measured from 10 subjects. The most prominent response, the cortically generated N1m, was investigated above the left and right hemisphere. We found, firstly, that the HRTF-based stimuli presented from different directions elicited contralaterally prominent N1m responses. Secondly, we found that cortical activity reflecting the processing of spatial sound stimuli was more pronounced in the right than in the left hemisphere.

Dose-dependent suppression by ethanol of transient auditory 40-Hz response.

RATIONALE: Acute alcohol (ethanol) challenge is known to induce various cognitive disturbances, yet the neural basis of the effect is poorly known. The auditory transient evoked gamma-band (40-Hz) oscillatory responses have been suggested to be associated with various perceptual and cognitive functions in humans; however, alcohol effects on auditory 40-Hz responses have not been investigated to date. OBJECTIVES: The objective of the study was to test the dose-related impact of alcohol on auditory transient evoked 40-Hz responses during a selective-attention task. METHODS: Ten healthy social drinkers ingested, in four separate sessions, 0.00, 0. 25, 0.50, or 0.75 g/kg of 10% (v/v) alcohol solution. The order of the sessions was randomized and a double-blind procedure was employed. During a selective attention task, 300-Hz standard and 330-Hz deviant tones were presented to the left ear, and 1000-Hz standards and 1100-Hz deviants to the right ear of the subjects (P=0. 425 for each standard, P=0.075 for each deviant). The subjects attended to a designated ear, and were to detect the deviants therein while ignoring tones to the other ear. RESULTS: The auditory transient evoked 40-Hz responses elicited by both the attended and unattended standard tones were significantly suppressed by the 0.50 and 0.75 g/kg alcohol doses. CONCLUSIONS: Alcohol suppresses auditory transient evoked 40-Hz oscillations already with moderate blood alcohol concentrations. Given the putative role of gamma-band oscillations in cognition, this finding could be associated with certain alcohol-induced cognitive deficits.

Electromagnetic recordings reveal latency differences in speech and tone processing in humans.

Human auditory electromagnetic brain responses to sinusoidal (tone) and speech stimuli (Finnish vowel /a/ with two different glottal excitations) were studied with whole-head magnetoencephalogram (MEG) and electrodes placed on the subject's scalp. The frequency and intensity of the sinusoidal stimulus were optimally adjusted to match the spectra of the speech stimuli. Both tone and speech sounds elicited a prominent electric N1-P2 and magnetic N1m-P2m response complex. N1 and P2 amplitudes were larger to speech sounds than those to the tone. This amplitude enhancement was not as evident in the N1m and P2m obtained in MEG. Both the N1(m) and P2(m) latency always peaked earlier for the tone than for the vowels. The source origin of N1m for both the tone and speech stimuli was in the auditory cortex, there being no significant location differences as a function of stimulus type. N1m in the right hemisphere was anterior to that on the left, and P2m was anterior to N1m in both hemispheres. Varying the perceptual quality of the vowels by changing their glottal excitations (from "soft" /a/ to "pressed" /A/) had no effect on the response amplitudes or latencies. Thus, the present results show that only the latency behavior of N1(m) and P2(m) reliably dissociates speech and tone processing in humans. The findings are discussed in relation to previous observations on cortical processing of sinusoidal and vowel sounds and with regard to the glottal excitation in speech processing.

Brain responses reveal the learning of foreign language phonemes.

Learning to speak a new language requires the formation of recognition patterns for the speech sounds specific to the newly acquired language. The present study demonstrates the dynamic nature of cortical memory representations for phonemes in adults by using the mismatch negativity (MMN) event-related potential. We studied Hungarian and Finnish subjects, dividing the Hungarians into a naive (no knowledge of Finnish) and a fluent (in Finnish) group. We found that the MMN for a contrast between two Finnish phonemes was elicited in the fluent Hungarians but not in the naive Hungarians. This result indicates that the fluent Hungarians developed cortical memory representations for the Finnish phoneme system that enabled them to preattentively categorize phonemes specific to this language.

A method for generating natural-sounding speech stimuli for cognitive brain research.

OBJECTIVE: In response to the rapidly increasing interest in using human voice in cognitive brain research, a new method, semisynthetic speech generation (SSG), is presented for generation of speech stimuli. METHODS: The method synthesizes speech stimuli as a combination of purely artificial processes and processes that originate from the natural human speech production mechanism. SSG first estimates the source of speech, the glottal flow, from a natural utterance using an inverse filtering technique. The glottal flow obtained is then used as an excitation to an artificial digital filter that models the formant structure of speech. RESULTS: SSG is superior to commercial voice synthesizers because it yields speech stimuli of a highly natural quality due to the contribution of the man-originating glottal excitation. CONCLUSION: The artificial modelling of the vocal tract enables one to adjust the formant frequencies of the stimuli as desired, thus making SSG suitable for cognitive experiments using speech sounds as stimuli.

Benzodiazepine temazepam suppresses the transient auditory 40-Hz response amplitude in humans.

To discern the role of the GABA(A) receptors in the generation and attentive modulation of the transient auditory 40-Hz response, the effects of the benzodiazepine temazepam (10 mg) were studied in 10 healthy social drinkers, using a double-blind placebo-controlled design. Three hundred Hertz standard and 330 Hz rare deviant tones were presented to the left, and 1000 Hz standards and 1100 Hz deviants to the right ear of the subjects. Subjects attended to a designated ear and were to detect deviants therein while ignoring tones to the other. Temazepam significantly suppressed the amplitude of the 40-Hz response, the effect being equal for attended and non-attended tone responses. This suggests involvement of GABA(A) receptors in transient auditory 40-Hz response generation, however, not in the attentive modulation of the 40-Hz response.

Separation of contamination caused by coil clicks from responses elicited by transcranial magnetic stimulation.

Transcranial magnetic stimulation (TMS) is accompanied with loud clicks that evoke auditory responses in the brain, confounding several types of TMS studies. We investigated the effects of these clicks with high-resolution EEG by applying TMS pulses at 3 magnitudes, with the coil placed either at 10 or 50 mm over the subjects' vertex and recording event-related potentials (ERPs). The clicks were found to elicit a positively displaced response at 150-250 ms post-TMS. Furthermore, clicks were found to interact with simultaneously presented auditory sinewave stimuli, resulting in an amplitude decrease in the auditory N1 response.