Short-term functional plasticity in the human auditory cortex: an fMRI study.

Applying functional magnetic resonance imaging (fMRI) techniques, hemodynamic responses elicited by sequences of pure tones of 950 Hz (standard) and deviant tones of 952, 954, and 958 Hz were measured before and 1 week after subjects had been trained at frequency discrimination for five sessions (over 1 week) using an oddball procedure. The task of the subject was to detect deviants differing from the standard stimulus. Frequency discrimination improved during the training session for three subjects (performance gain: T+) but not for three other subjects (no performance gain: T-). Hemodynamic responses in the auditory cortex comprising the planum temporale, planum polare and sulcus temporalis superior significantly decreased during training only for the T+ group. These activation changes were strongest for those stimuli accompanied by the strongest performance gain (958 and 954 Hz). There was no difference with respect to the hemodynamic responses in the auditory cortex for the T- group and the control group (CO) who did not received any pitch discrimination training. The results suggest a plastic reorganization of the cortical representation for the trained frequencies which can be best explained on the basis of 'fast learning' theories.     

Effects of brief discrimination-training on the auditory N1 wave

We determined whether the human N1 evoked by tones with different frequencies might be affected by a brief discrimination-training at one specific frequency. During 1 h training, subjects learned to discriminate a 1062 Hz tone from another tone. Before and after training, subjects heard for 26 min tones with a frequency of 1000 Hz, replaced every sixth one by test tones with frequencies randomly and equiprobably chosen as 835, 886, 941, 1000, 1062, 1128 or 1198 Hz. The N1 to the test tone was larger when its frequency was further from the repeating frequency. After training N1 s were attenuated to all tones except the trained and repeated ones, indicating a refractory frequency effect, long-term habituation, and sensitization to the repeated and trained tones.     

Neuromagnetic mismatch fields to single and paired tones.

In 8 subjects we recorded multichannel magnetic responses to pitch changes in single 50 msec tones and in tone pairs (oddball paradigm; interstimulus interval 745 msec). Either "A" (1 kHz) was standard (90%) and "B" (1.2 kHz) deviant (10%), or "AA" was standard and "AB" deviant in pairs with onset asynchrony of 75 msec. Subject did not pay attention to the tones. A mismatch field (MMF) was evident in responses to deviants with an equivalent source in the supratemporal auditory cortex, about 1 cm anterior to that for N100m. The MMF source was 3-fold stronger for tone pairs than for single tones.     

The mismatch negativity to frequency deviant stimuli during natural sleep

Eight subjects spent a single night in the sleep laboratory. Event-related potentials (ERPs) were recorded during the presentation of two auditory ‘oddball’ stimulus conditions in which tonal frequency was manipulated. In the first condition, 1000 Hz ‘standard’ and 2000 Hz ‘deviant’ tones were presented. In the second condition, the deviant tone was reduced to 1050 Hz. In both conditions, deviant probability was 0.2. Stimuli were presented every 600 ms during wakefulness and stages 2, 4, and REM of sleep. A distinctive N1 wave was visible in both stimulus conditions when the subject was awake. The deviant stimuli elicited a ‘mismatch negativity’ (MMN) that inverted in polarity at the mastoid. In REM sleep, an N1 and a MMN were also elicited in both conditions. In the large deviance condition, the MMN had a slightly attenuated amplitude and was shorter in duration while in the small deviant condition, its peak latency was unusually early. Neither the N1 nor the MMN could be recorded in non-REM sleep.     

Rapid change of tonotopic maps in the human auditory cortex during pitch discrimination.

OBJECTIVE: To study early cognitive processes and hemispheric differences in the primary auditory cortex during selective attention. METHODS: We measured auditory evoked magnetic fields (AEFs) to 400 and 4000 Hz tone pips that were randomly presented at the right or left ear. Subjects paid attention to target stimuli during pitch (high or low) or laterality (left or right) discrimination tasks. In the control session, 400 or 4000 Hz tone alone was presented at the left or right ear. We calculated the location and strength of N100m dipole for 400 and 4000 Hz tones, based on the AEFs obtained from the hemisphere contralateral to the stimulated ear. RESULTS: N100m amplitude increased in both hemispheres in pitch or laterality discriminating conditions. N100m latency also shortened during selective attention. The N100m dipole distance between 400 and 4000 Hz tones was enlarged, especially in the right auditory cortex during pitch discrimination task, but was unchanged during the laterality discrimination task. CONCLUSIONS: We conclude that these dynamic changes in the N100m dipole reflect short-term plastic changes in the primary auditory cortex, supporting early selection models. SIGNIFICANCE: This work is the first to disclose short-term plastic changes during pitch discrimination in the human auditory cortex based on the analysis of magnetoencephalography.     

Attentional modulation in the detection of irrelevant deviance: a simultaneous ERP/fMRI study

Little is known about the neural mechanisms that control attentional modulation of deviance detection in the auditory modality. In this study, we manipulated the difficulty of a primary task to test the relation between task difficulty and the detection of infrequent, task-irrelevant deviant (D) tones (1,300 Hz) presented among repetitive standard (S) tones (1,000 Hz). Simultaneous functional magnetic resonance imaging (fMRI)/event-related potentials (ERPs) were recorded from 21 subjects performing a two-alternative forced-choice duration discrimination task (short and long tones of equal probability). The duration of the short tone was always 50 msec. The duration of the long tone was 100 msec in the easy task and 60 msec in the difficult task. As expected, response accuracy decreased and response time (RT) increased in the difficult compared with the easy task. Performance was also poorer for D than for S tones, indicating distraction by task-irrelevant frequency information on trials involving D tones. In the difficult task, an amplitude increase was observed in the difference waves for N1 and P3a, ERP components associated with increased attention to deviant sounds. The mismatch negativity (MMN) response, associated with passive deviant detection, was larger in the easy task, demonstrating the susceptibility of this component to attentional manipulations. The fMRI contrast D > S in the difficult task revealed activation on the right superior temporal gyrus (STG) and extending ventrally into the superior temporal sulcus, suggesting this region's involvement in involuntary attention shifting toward unattended, infrequent sounds. Conversely, passive deviance detection, as reflected by the MMN, was associated with more dorsal activation on the STG. These results are consistent with the view that the dorsal STG region is responsive to mismatches between the memory trace of the standard and the incoming deviant sound, whereas the ventral STG region is activated by involuntary shifts of attention to task-irrelevant auditory features.     

The habituation of event-related potentials to speech sounds and tones

We examined the short- and long-term habituation of auditory event-related potentials (ERPs) elicited by tones, complex tones and digitized speech sounds (vowels and consonant-vowel-consonant syllables). Twelve different stimuli equated in loudness and duration (300 msec) were studied. To examine short-term habituation stimuli were presented in trains of 6 with interstimulus intervals of 0.5 or 1.0 sec. The first 4 stimuli in a train were identical standards. On 50% of the trains the standard in the 5th position was replaced by a deviant probe stimulus, and on 20% of the trains the standard in the 6th position was replaced by a target, a truncated standard that required a speeded button press response. Short-term habituation (STH) was complete by the third stimulus in the train and resulted in amplitude decrements of 50-75% for the N1 component. STH was partially stimulus specific in that amplitudes were larger following deviant stimuli in the 5th position than following standards. STH of the N1 was more marked for speech sounds than for loudness-matched tones or complex tones at short ISI. In addition, standard and deviant stimuli that differed in phonetic structure showed more cross-habituation than did tones or complex tones that differed in frequency. This pattern of results suggests that STH is a function of the acoustic resemblance of successive stimuli. The long-term habituation (LTH) of the ERP was studied by comparing amplitudes across balanced 5.25 m stimulus blocks over the course of the experiment. Two types of LTH were observed. The N1 showed stimulus-specific LTH in that N1 amplitudes declined during the presentation of a stimulus, but returned to control levels when a different stimulus was presented in the subsequent condition. In contrast, the P3 elicited by the deviant stimuli showed non-specific LTH, being reduced across successive blocks containing different stimuli. P3s elicited by target stimuli remained stable in amplitude.     

Frequency discrimination at different frequency levels as indexed by electrophysiological and behavioral measures

The present study systematically compared the neural and behavioral accuracy of discriminating a frequency change ("deviant") in a repetitive tone ("standard") across a frequency range of 250-4000 Hz. The sound structure (pure sinusoidal vs. harmonically rich tones) and the magnitude of frequency change (2.5%, 5%, 10%, 20%) were also varied. The accuracy of neural frequency-change detector was determined by comparing the auditory event-related potentials (ERP) elicited by deviant and standard stimuli in the absence of attention. In a separate behavioral task, subjects were to indicate when they noticed a frequency change. The ranges of the across-subject means of ERP parameters across the conditions were: the mismatch negativity (MMN) amplitude -0.9 to -4.9 microV, latency 125-218 ms, the P3a amplitude 0.3-3.2 microV, latency 239-304 ms. The ERP latency was shortest for the standard-stimulus frequency from 1000 to 2000 Hz suggesting that automatic frequency discrimination was the most accurate in that range. The ERP latencies and amplitudes correlated with the hit rate (HR) and reaction time (RT), with highest correlation found between the MMN amplitude and the HR (r=0.8). The harmonical tones elicited MMN and P3a with shorter latencies and larger amplitudes, than did pure sinusoidal tones in all frequency bands. The results may have implication to pitch-perception theories.     

Functional hemispheric asymmetries in humans: electrophysiological evidence from preterm infants

In recent years, magnetic resonance imaging has allowed researchers to individuate the earlier morphological development of the right hemisphere compared with the left hemisphere during late‐gestational development. Anatomical asymmetry, however, does not necessarily mean functional asymmetry, and whether the anatomical differences between hemispheres at this early age are paralleled by functional specialisations remains unknown. In this study, the presence of lateralised electrical brain activity related to both pitch detection and discrimination was investigated in 34 prematurely‐born infants [24–34 gestational weeks (GWs)] all tested at the same post‐conceptional age of 35 weeks. By means of a frequency–change oddball experimental paradigm, with ‘standard’ tones at 1000 Hz (P = 90%) and ‘deviant’ tones at 2000 Hz (P = 10%), we were able to record higher right event‐related potential activity in the interval windows between 350 and 650 ms after stimulus onset. An explorative hierarchical cluster analysis confirmed the different distribution of the hemispheric asymmetry score in newborns < 30 weeks old. Here, we show electrophysiological evidence of the early functional right lateralisation for pitch processing (detection and discrimination) arising by 30 GWs, but not before, in preterm newborns despite the longer environmental sensorial experience of newborns < 30 GWs. Generally, these findings suggest that the earlier right structural maturation in foetal epochs seems to be paralleled by a right functional development.     

Evoked magnetic responses of the human auditory cortex to minor pitch changes: localization of the mismatch field.

The neuromagnetic source localizations of the auditory M100 and the mismatch field (MMF) were studied using a large-array biomagnetometer. Standard tones of 1000 Hz and deviant tones of 1050 Hz were delivered with 90% and 10% probability, respectively. Wave forms of the derived MMF were computed by examining difference wave forms between the responses to the deviants and the responses to the standards preceding (D-P) and following (D-F) the deviants as well as to all remaining standards (D-A). The subset of standards preceding the deviants was used for a more realistic comparison with the set of deviants (having the same number of epochs and a similar signal-to-noise ratio), while the subset of standards following the deviants served to answer the question whether those standards also elicit an MMF. The MMF deflections were compared with each other, with the "native" MMF occurring in response to the deviants, and with wave M100. (The MMF as it appears in the unprocessed response to the deviants was termed "native" for an easy distinction from the "derived" MMF.) Our results demonstrate a distinct MMF deflection, corresponding in latency to the simultaneously recorded fronto-central electrical MMN. Source analysis, using a single moving dipole model, showed the same spatial localization for the native MMF and for the different derived MMFs. The MMF source location turned out to be significantly anterior, medial and inferior relative to the sources of the M100. The present data also demonstrate that a minor frequency deviation may not activate measurably different M100 generators, yet be sufficient to trigger the nearby but spatially distinct mismatch generator.     

The vanishing point of the mismatch negativity at sleep onset.

OBJECTIVE: To determine when the mismatch negativity (MMN) disappears at sleep onset, event-related potentials (ERPs) were recorded continuously from wakefulness to sleep. METHODS: Ten healthy young students were told to fall asleep ignoring the tones presented through a loudspeaker above their head. Standard (1000 Hz, P=0.90), high deviant (1200 Hz, P=0.05), and low deviant (1050 Hz, P=0.05) tones were presented in a quasirandom order with a fixed stimulus onset asynchrony of 500 ms. ERP waveforms were obtained separately for 5 successive stages characterized by typical electroencephalographic (EEG) patterns of the sleep onset period. The EEG staging was made manually with very short (5 s) scoring epochs. RESULTS: The MMN appeared in wakefulness and in the early phase of stage 1 sleep (EEG stage II) but disappeared when low-voltage theta waves emerged after alpha flattening (EEG stage III). Instead, P240 and N360 developed particularly for high deviant tones. CONCLUSIONS: Concurrently with the disappearance of alpha waves, the automatic change detection system in wakefulness seems to stop operating and a different sleep-specific system becomes dominant.     

Priority of repetitive adaptation to mismatch response following undiscriminable auditory stimulation: a magnetoencephalographic study

We analysed two different neural mechanisms related to the unconscious processing of auditory stimulation, neural adaptation and mismatch negativity (MMN), using magnetoencephalography in healthy non-musicians. Four kinds of conditioning stimulus (CS): white noise, a 675-Hz pure tone, and complex tones with six (CT6) and seven components (CT7), were used for analysing neural adaptation. The seven spectral components of CT7 were spaced by 1/7 octaves between 500 and 906 Hz on the logarithmic scale. The CT6 components contained the same spectral components as CT7, except for the center frequency, 675 kHz. Subjects could not distinguish CT6 from CT7 in a discrimination test. A test stimulus (TS), a 675-Hz tone, was presented after CS, and the effects of the presence of the same 675-Hz frequency in the CS on the magnetoencephalographic response elicited by TS was evaluated. The P2m component following CT7 was significantly smaller in current strength than that following CT6. The equivalent current dipole for P2m was located approximately 10 mm anterior to the preceding N1m. This result indicated that neural adaptation was taking place in the anterior part of the auditory cortex, even if the sound difference was subthreshold. By contrast, the magnetic counterpart of the MMN was not recorded when CT6 and CT7 were used as standard and deviant stimuli, respectively, being consistent with the discrimination test. In conclusion, neural adaptation is considered to be more sensitive than our consciousness or the MMN, or is caused by an independent mechanism.     

Neural mechanisms of the time-order error: an MEG study

The time-order error (TOE) refers to the influence of presentation order on performance accuracy in a discrimination task. Despite it being a well-documented perceptual bias, the underlying mechanisms have not been studied. In this study, observers were trained on a two-interval forced-choice procedure. The stimuli presented for discrimination were a standard, consisting of four tones presented at a 5-Hz rate, and targets, consisting of various rates higher than 5 Hz. Psychometric functions were measured for discrimination of the trained standard and targets, a novel standard of 13 Hz with higher target rates; and the trained 5 Hz standard with novel targets with rates below 5 Hz. Discrimination did not improve with training; in fact, accuracy declined when standard was presented in the first interval during the session, resulting in a TOE. The TOE was specific to the 5-Hz standard generalizing to the novel targets slower than 5 Hz, but not to the 13-Hz STANDARD. Analysis of the event-related magnetic field responses (ERFs) revealed a waveform to the whole stimulus, rather than to each tone in the train. Although ERFs in the second interval were attenuated independent of stimulus type, the M300 component in the second interval was attenuated only when the standard was first, but remained of equivalent magnitude when the standard was second. This was observed only in the two 5-Hz conditions. Combined, these results suggest that the TOE reflects the emergence of an internal representation of the standard, and that the M300 is potentially a neural correlate of plasticity.     

Enhanced contrast sensitivity in auditory cortex as cats learn to discriminate sound frequencies

To better understand the nature and time course for learning-induced cortical reorganization, we examined frequency-specific changes in auditory cortex as cats gradually improved at a difficult sound frequency discrimination task. Three adult cats were trained to discriminate between a tone pip at a fixed target frequency (S-) and a higher deviant frequency (S+). An adaptive training schedule led to an efficient estimate of the frequency discrimination threshold (FDT), which was used to track daily performance. Each cat was also implanted with an array of microwires in auditory cortex. Tone pips with different frequency and amplitude were used to map receptive fields. Onset responses were correlated with training time and the cat's ability to discriminate frequencies. Although lifetime of the neural implants varied among cats, each provided sufficient neural recording to relate at least 3 weeks of learning to response changes in the cortex. An improved FDT was associated with a differential decrease in response strength between the S- frequency and S+ frequencies. Response to the training frequencies gradually located in a local minimum compared to adjacent frequencies (p < 0.001, Cohen's d=0.50). Cortical changes were consistent with a theory of bimodal generalization that enhances stimulus classification by reducing similarity between reinforced and nonreinforced stimuli. Such a strategy may be especially appropriate during an early stage of learning to discriminate similar sounds and differ from later strategies required for fine discrimination.     

Auditory event-related potentials in panic disorder

To investigate the psychophysiological features of panic disorder (PD), we recorded auditory event-related potentials (ERPs) in 12 patients with PD meeting the DSM-IV criteria and in 12 age-matched normal controls. The ERPs were recorded during a standard two-tone discrimination task (oddball task). The probabilities of the rare target (1200 Hz) and frequent non-target tones (1000 Hz) were 15 and 85%, respectively. The subjects were required to press a button in response to the rare target tones. Scalp electroencephalograms were recorded from Fz, Cz, Pz, C3, and C4. The State-Trait Anxiety Inventory and Manifest Anxiety Scale scores were assessed for clinical evaluation. Analysis of variance revealed that the N1 and N2 amplitudes for target tones and the N1 amplitude for non-target tones were significantly larger in the PD patients than those in the controls. The two groups did not differ significantly in P3 latency and amplitude. The larger N1 and N2 amplitudes in the PD patients are suggestive of alteration of early information processing in PD.     

Dopamine modulates involuntary attention shifting and reorienting: an electromagnetic study

Objective: Dopaminergic function has been closely associated with attentional performance, but its precise role has remained elusive.Methods: Electrophysiological and behavioral methods were used to assess the effects of dopamine D2-receptor antagonist haloperidol on involuntary attention shifting using a randomized, double-blind, placebo-controlled cross-over design. Eleven subjects were instructed to discriminate equiprobable 200 and 400 ms tones in a forced-choice reaction-time (RT) task during simultaneous measurement of whole-head magnetoencephalography and high-resolution electroencephalography.Results: Occasional changes in task-irrelevant tone frequency (10% increase or decrease) caused marked distraction on behavioral performance, as shown by significant RT increases to deviant stimuli and subsequent standard tones. Furthermore, while the standard tones elicited distinct P1–N1–P2–N2–P3 waveforms, deviant tones elicited additional mismatch negativity (MMN), P3a, and reorienting negativity (RON) responses, indexing brain events associated with involuntary attention shifting. While haloperidol did not affect the source loci of the responses of magnetic N1 and MMN, the amplitude of the electric P3a and that of RON were significantly reduced and the latency of magnetic RON were delayed following haloperidol administration.Conclusions: The present results suggest that dopamine modulates involuntary attention shifting to task-irrelevant deviant events. It appears that dopamine may disrupt the subsequent re-orienting efforts to the relevant task after distraction.     

An electrophysiological and behavioral investigation of involuntary attention towards auditory frequency,duration and intensity changes

We measured behavior and event-related brain potentials (ERPs) in 12 subjects performing on an audio-visual distraction paradigm to investigate the cerebral mechanisms of involuntary attention towards stimulus changes in the acoustic environment. Subjects classified odd/even numbers presented on a computer screen 300 ms after the occurrence of a task-irrelevant auditory stimulus, by pressing the corresponding response button. Auditory stimuli were standard tones (600 Hz, 200 ms, 85 dB; P=0.8) or deviant tones (P=0.2), these differing from the standard either in frequency (700 Hz), duration (50 ms) or intensity (79 dB), in separate blocks. In comparison to performance to visual stimuli following the standard tones, reaction time increased by 24 ms (F(1,11)=10.91, P<0.01) and hit rate decreased by 4.6% (F(1,11)=35.47, P<0.001) to visual stimuli following the deviant tones, indicating behavioral distraction. ERPs revealed the mismatch negativity (MMN) elicited to deviant tones, which was larger for the duration deviant than for the frequency and intensity deviants (F(2,22)=19.43, P<0.001, epsilon =0.83), and which had different scalp distribution for all three deviant conditions (F(16,176)=2.40, P<0.05, epsilon =0.12). As the shorter duration and softer intensity deviant tones were unlikely to engage fresh neurons responding to their specific physical features, the present results indicate that a genuine change detection mechanism is involved in triggering attention switching towards sound changes, and suggest a largely distributed neural network of the auditory cortex underlying such involuntary attention switching.     

Attentional deficits in patients with obstructive sleep apnea syndrome: an event-related potential study.

OBJECTIVE: Patients with obstructive sleep apnea syndrome (OSAS) show cognitive deficits, vigilance alteration and attentional decline. The aim of this study was to use event-related potentials (ERP) to further document the attentional impairments in these patients. METHODS: Twelve OSAS patients and 12 age-matched controls underwent the ERP task which consisted in the presentation of short (50ms, 50%) and long tones (400ms, 50%). For these two categories, 90% were standard (1000Hz) and 10% were deviant tones (750 or 1250Hz). Subjects had to discriminate short and long tones by a motor response. RESULTS: OSAS patients had a sustained and delayed P300 in comparison with control subjects following standard tones (p<0.05). A reduction in amplitude was found in OSAS patients for the P3a obtained by the subtraction of standard from deviant tones (p<0.05). No group difference was observed for N1, mismatch negativity and reorienting negativity components. CONCLUSIONS: Apneas and hypopneas produce deficits related to involuntary attentional switch and stimulus classification processing. SIGNIFICANCE: The changes observed in P3a and P300 components further support the hypothesis that attentional deficits play a pivotal role in cognitive deficits noted in OSAS.     

The mismatch negativity and the P3a components of the auditory event-related potentials in autistic low-functioning subjects.

OBJECTIVE: In order to understand better the psychophysiological basis of auditory processing abnormalities in autism, we decided to study two automatic components of the auditory event-related potentials (ERPs): the mismatch negativity (MMN)--a component of the ERP which is recorded when, during repetitive auditory stimulation, rare changes are introduced--and the novelty-related P3a which is recorded as a response to unexpected novel events occurring in a sequence of repetitive stimuli. METHODS: Ten male subjects, mean age 12.3 years (SD 4.95), affected by autism and mental retardation were admitted to this study. All patients were also mentally retarded. Ten normal male subjects, mean age 12.2 years (SD 3.94), were used as controls. Auditory evoked potentials were recorded from 19 scalp electrodes (10-20 system), and stimuli were presented in sequences consisting of 2000 tones (70 dB, ISI=800 ms). Three types of stimuli were presented: (1) standard stimuli (1000 Hz tones, 80% of total stimuli), (2) deviant stimuli (1300 Hz tones, 10% of total stimuli), and (3) novel stimuli (complex and non-monotonal, 10% of total stimuli). To quantify the MMN, the evoked response to the standard tones was subtracted from the corresponding deviant stimulus response and its amplitude and latency at peak were measured over Fz, Cz and Pz; similarly, the P3a component of the ERP was obtained by subtracting the response to the standard tone from that to the novel stimuli and its amplitude and latency at peak were measured over Fz, Cz and Pz. Also, the amplitude and latency at peak for the N1 component of the auditory evoked potential obtained with the standard stimuli were measured over Fz, Cz and Pz. The correlation between age and MMN and P3a amplitude was also analyzed. RESULTS: N1 showed significantly shorter latencies in the autistic groups. MMN elicited by deviant stimuli, but not that elicited by novel stimuli, was found to be significantly larger in autistic children than in normal controls. P3a showed higher amplitude in autistic subjects than in normal controls during childhood; the opposite was observed during young adulthood. DISCUSSION: Our findings indicate that significant changes in ERPs can also be seen in non-cooperative individuals with autism and mental retardation, which might be different from the changes already reported for high-functioning autistic subjects and deserve further insight. These changes show developmental modifications that should be taken into consideration when analyzing data from autistic subjects.     

Dysfunction in early auditory processing in major depressive disorder revealed by combined MEG and EEG

BACKGROUND: Patients with major depressive disorder (MDD) show impairments in cognitive functions. However, neural mechanisms underlying these disturbances are poorly understood. We investigated whether MDD affects neural mechanisms of involuntary attention studied by auditory evoked potentials (AEPs) and auditory evoked magnetic fields (AEFs). METHODS: AEPs and AEFs were studied in a passive odd-ball paradigm in 13 drug-free patients with unipolar MDD during an acute episode and 12 age-and sex-matched healthy subjects. Auditory responses to monaurally presented frequent "standard" tones, infrequent "deviant" tones (10% and 20% frequency change) and occasional "novel" sounds (complex sounds) were simultaneously recorded with whole-head magnetoencephalography (MEG) and electroencephalography (EEG). RESULTS: P1 and P1m latencies were decreased in patients with MDD, compared with those in healthy subjects. Further, the mismatch negativity amplitude to the 10% frequency deviance in the EEG, but not in the MEG, was increased in MDD. We observed no differences in N1/N1m and P3a responses in the MEG and EEG. The magnitude of decrease in P1/P1m latency correlated negatively with the severity of depression in the patients. CONCLUSIONS: Early auditory processing is impaired in patients with MDD during an acute episode, probably reflecting dysfunctional frontotemporal neural circuits. These dysfunctions may contribute to the cognitive disturbances observed in people with MDD.