Phonetic mismatch negativity predicts verbal memory deficits in schizophrenia

Deficits in auditory sensory memory at the electrophysiological level as indexed by mismatch negativity and those in auditory verbal memory at the neuropsychological level have been independently demonstrated in previous studies of schizophrenia. We predicted a specific association between these indices in schizophrenia. Mismatch negativities elicited by change in tone duration and phoneme duration were recorded in 23 schizophrenia patients, who were also evaluated for auditory verbal memory and executive function. Lower amplitude of mismatch negativity under the phoneme-duration condition was significantly associated with worse verbal memory. Phoneme-duration mismatch negativity was not correlated with executive function, nor was tone-duration mismatch negativity correlated with verbal memory. These results suggest that electrophysiological auditory sensory memory dysfunction underlies the basis for neuropsychological auditory verbal memory deficits in schizophrenia.     

Extracting rules: early and late mismatch negativity to tone patterns

The auditory processing of physical stimulus features can be measured by the mismatch negativity. Past studies have shown that higher-order stimulus features also elicit a mismatch negativity. In some studies, a second component, termed late mismatch negativity, has been observed; yet the functional significance of this component remains unclear. We tested two-tone-pattern stimuli following an abstract rule in healthy adults. As expected, the tone pattern elicited a significant mismatch negativity peaking at 146 ms but a significant late mismatch negativity at around 340 ms was also observed. These findings show that the violation of an abstract rule elicits an early and late mismatch negativity. The late mismatch negativity might be triggered on the basis of auditory rule extraction processes and reflect a transfer of rules to the long-term memory.     

Audiovisual phonological mismatch produces early negativity in auditory cortex

During silent reading, visual information provided by letters is converted to auditory information in the mind. The purpose of this study was to identify the primary locus for auditory verbal imagery in the brain. Neuromagnetic recording was obtained from 10 right-handed study participants, who were instructed to identify infrequently occurring phonological mismatches between a random-ordered sequence of syllable sounds and a visually presented syllabogram sequence. The activity difference in early latency, calculated by subtracting the averaged responses to matched syllables from the averaged responses to mismatched syllables, showed a spatiotemporal profile strikingly similar to that of mismatch negativity. Auditory imagery of forthcoming verbal sounds may establish a memory trace as a template for imagery-based mismatch negativity generation in the auditory cortex.     

A distributed cortical network for auditory sensory memory in humans

Auditory sensory memory is a critical first stage in auditory perception that permits listeners to integrate incoming acoustic information with stored representations of preceding auditory events. Here, we investigated the neural circuits of sensory memory using behavioral and electrophysiological measures of auditory processing in patients with unilateral brain damage to dorsolateral prefrontal cortex, posterior association cortex, or the hippocampus. We used a neurophysiological marker of an automatic component of sensory memory, the mismatch negativity (MMN), which can be recorded without overt attention. In comparison with control subjects, temporal-parietal patients had impaired auditory discrimination and reduced MMN amplitudes with both effects evident only following stimuli presented in the ear contralateral to the lesioned hemisphere. This suggests that auditory sensory memories are predominantly stored in auditory cortex contralateral to the ear of presentation. Dorsolateral prefrontal damage impaired performance and reduced MMNs elicited by deviant stimuli presented in either ear, implying that dorsolateral prefrontal cortices have a bilateral facilitatory effect on sensory memory storage. Hippocampal lesions did not affect either performance or electrophysiological measures. The results provide evidence of a temporal-prefrontal neocortical network critical for the transient storage of auditory stimuli.     

Auditory sensory memory in 2-year-old children: an event-related potential study

Auditory sensory memory is assumed to play an important role in cognitive development, but little is known about it in young children. The aim of this study was to estimate the duration of auditory sensory memory in 2-year-old children. We recorded the mismatch negativity in response to tone stimuli presented with different interstimulus intervals. Our findings suggest that in 2-year-old children the memory representation of the standard tone remains in the sensory memory store for at least 1 s but for less than 2 s. Recording the mismatch negativity with stimuli presented at various interstimulus intervals seems to be a useful method for studying the relationship between auditory sensory memory and normal and disturbed cognitive development.     

A modified parallel paradigm for clinical evaluation of auditory echoic memory

We established a new parallel paradigm for mismatch negativity by presenting repetitive trains of three consonant-vowel syllables and those of three sinusoidal tones alternately. Magnetoencephalography was performed to test the new method, and mismatch negativities in six study participants with normal hearing were compared with the results of the conventional oddball paradigm. Peak amplitude and latencies of mismatch negativity showed no significant difference between the methods. The maximum amplitude in short memory probe interval of 1.0 s was significantly larger than in long memory probe interval of 3.0 s, demonstrating decay in auditory echoic memory caused by a prolonged memory probe interval. The new method facilitated simultaneous evaluation of mismatch negativity with various stimuli in a shorter period.     

Sound presentation rate is represented logarithmically in human cortex

The encoding of temporal information is critical to auditory processing. Since the mismatch negativity component of the auditory event-related brain potential is thought to reflect properties of auditory sensory memory, we used it to examine the representation of acoustic time intervals in the human cortex. The mismatch negativity occurs in response to deviations in acoustic regularities, which are stored in sensory memory. We used 16 stimulus conditions, randomly presenting short trains of tones with fixed onset-to-onset intervals of 100, 200, 300 or 400 ms (all tones in the study were identical). The first four intervals between the tones established the acoustic regularity on each train (i.e. the 'standard'). The fifth tone in each train was preceded by an interval that varied randomly among the same four intervals. If this interval was different from the standard for that trial, it violated the acoustic regularity (i.e. it was a 'deviant'). The mismatch response to the fifth tone differed significantly among stimulus conditions and was proportional to the absolute value of the logarithm of the deviant/standard interval ratio. This indicates that short acoustic time intervals are represented with a ratio scale in the human cortex. When the fifth tone occurred 100 ms after the fourth, it elicited a somewhat different, although proportional response, supporting the hypothesis that a special integration mechanism may exist for very short time intervals.     

Deficits in auditory and visual context-dependent processing in schizophrenia: defining the pattern

BACKGROUND: Brain mechanisms underlying deficits in precision of transient memory storage in schizophrenia were investigated using a combined behavioral and event-related potential approach. Performance was measured simultaneously in 2 tasks: an AX-type visual continuous performance test (AX-CPT), which required subjects to press a button whenever they saw a letter A followed by a letter X, and a mismatch negativity paradigm. The AX-CPT is designed to assess prefrontal function, whereas mismatch negativity assesses functioning of the auditory sensory memory system. METHODS: Subjects were 17 patients with chronic schizophrenia, 13 with recent-onset schizophrenia, and 20 normal comparison subjects. Potentials were recorded from 36 scalp locations in response to cue stimuli in the CPT and to duration- and pitch-deviant stimuli in the mismatch negativity paradigm. Behavioral measures including responses to incorrect cue-target sequences that should have been ignored ("false alarms") were analyzed as a function of cue-target interval. RESULTS: Chronic and recent-onset schizophrenic patients showed significantly decreased mismatch negativity amplitude but normal latency and topography. In the CPT, patients showed significantly higher rates of false alarms following incorrect cues ("BX" errors) and decreased rates of correct detections. Impaired performance correlated with decreased frontocentral event-related potential activation to incorrect cues that was manifest within several hundred milliseconds of cue presentation. All groups performed worse with increasing cue-target intervals. Patients were no more affected by increased cue-target interval than were controls. CONCLUSIONS: Schizophrenic patients are significantly impaired in their ability to form and utilize transient memory traces to guide behavior. These deficits are associated with failures of cortical activation occurring within several hundred milliseconds of stimulus presentation. A similar pattern of deficit is observed across sensory and cognitive systems. Arch Gen Psychiatry. 2000;57:1131-1137.     

Superior pre-attentive auditory processing in musicians.

The present study focuses on influences of long-term experience on auditory processing, providing the first evidence for pre-attentively superior auditory processing in musicians. This was revealed by the brain's automatic change-detection response, which is reflected electrically as the mismatch negativity (MMN) and generated by the operation of sensoric (echoic) memory, the earliest cognitive memory system. Major chords and single tones were presented to both professional violinists and non-musicians under ignore and attend conditions. Slightly impure chords, presented among perfect major chords elicited a distinct MMN in professional musicians, but not in non-musicians. This demonstrates that compared to non-musicians, musicians are superior in pre-attentively extracting more information out of musically relevant stimuli. Since effects of long-term experience on pre-attentive auditory processing have so far been reported for language-specific phonemes only, results indicate that sensory memory mechanisms can be modulated by training on a more general level.     

Organization of sequential sounds in auditory memory

A repeating five-tone pattern was presented at several stimulus rates (200, 400, 600, and 800 ms onset-to-onset) to determine at what temporal proximity the five-tone repeating unit would be represented in memory. The mismatch negativity component of event-related brain potentials was used to index how the sounds were organized in memory when participants had no task with the sounds. Only at the 200-ms onset-to-onset pace was the five-tone sequence unitized in memory. At presentation rates of 400 ms and above, the regularity (a different frequency tone occurred every fifth tone) was not detected and mismatch negativity was elicited by these tones in the sequence. The results show that temporal proximity plays a role in unitizing successive sounds in auditory memory. These results also suggest that global relationships between successive sounds are represented at the level of auditory cortices.     

Preattentive detection of nonsalient contingencies between auditory features

Extraction of contingencies between features of successive auditory stimuli was studied by exploiting the mismatch negativity component of the event-related potential. According to the rules hidden in the stimulus sequences, one stimulus feature (duration) predicted another feature (pitch) of the next stimulus. Occasional deviant stimuli, violating the rules, elicited a mismatch negativity although the participants were ignoring the stimuli. Mismatch negativity was also elicited when the participants tried to detect the deviant stimuli. Their detection performance, however, was poor and on the basis of subsequent interviews, they were not consciously aware of the rules. The results suggest that contingencies across-features of successive stimuli are extracted already at the early preattentive level in the auditory sensory memory.     

Change detection and difference detection of tone duration discrimination

An event-related potential called mismatch negativity is known to exhibit physiological evidence of sensory memory. Mismatch negativity is believed to represent complicated neuronal mechanisms in a variety of animals and in humans. We employed the auditory oddball paradigm varying sound durations and observed two types of duration mismatch negativity in anesthetized guinea pigs. One was a duration mismatch negativity whose increase in peak amplitude occurred immediately after onset of the stimulus difference in a decrement oddball paradigm. The other exhibited a peak amplitude increase closer to the offset of the longer stimulus in an increment oddball paradigm. These results demonstrated a mechanism to percept the difference of duration change and revealed the importance of the end of a stimulus for this perception.     

Time may be compressed in sound representation as replicated in sensory memory

The flow of time in the real world may differ from the one in the neural representation of auditory scene stored in the sensory memory, because the encoded information is free from the rule of actual time. The sensory memory underlying the automatic discriminative system is reflected by the mismatch negativity (MMN). The time-wise image of preceding sounds is integrated into the sensory memory as a 160-170 ms epoch. We measured the mismatch field (MMNm) and the reaction time responding to the omitted segments incorporated into a complex sound. The main result was that the encoded period from early to late omitted segment was shorter than the actual one, suggesting that time may be compressed in the sound representation.     

Development of auditory sensory memory from 2 to 6 years: an MMN study

Short-term storage of auditory information is thought to be a precondition for cognitive development, and deficits in short-term memory are believed to underlie learning disabilities and specific language disorders. We examined the development of the duration of auditory sensory memory in normally developing children between the ages of 2 and 6 years. To probe the lifetime of auditory sensory memory we elicited the mismatch negativity (MMN), a component of the late auditory evoked potential, with tone stimuli of two different frequencies presented with various interstimulus intervals between 500 and 5,000 ms. Our findings suggest that memory traces for tone characteristics have a duration of 1-2 s in 2- and 3-year-old children, more than 2 s in 4-year-olds and 3-5 s in 6-year-olds. The results provide insights into the maturational processes involved in auditory sensory memory during the sensitive period of cognitive development.     

Association between reduced duration mismatch negativity (MMN) and raised temporal discrimination thresholds in schizophrenia.

OBJECTIVE: The event-related potential known as mismatch negativity (MMN) is elicited whenever the auditory system detects a change against an invariant background of stimulation. A reduction in mismatch negativity is well established in schizophrenia. The present study explored the association between reduced duration mismatch negativity in schizophrenia and behavioural measures of temporal discrimination. METHOD: Mismatch negativity amplitude to duration increments (125 vs. 50 ms) was compared between individuals with schizophrenia and healthy controls. Mismatch negativity amplitude was also related to two behavioural measures of temporal discrimination (silent and filled intervals) for detecting changes in stimuli of similar duration. RESULTS: Patients produced higher discrimination threshold estimates and smaller amplitude mismatch negativity responses to temporally deviant stimuli. Temporal discrimination thresholds correlated with the amplitude of the phase reversal in mismatch negativity at the left mastoid such that patients who produced the highest thresholds produced the smallest mismatch response. CONCLUSIONS: Imprecise representations of the temporal properties of auditory stimuli can account for some of the reduction in mismatch negativity amplitude in some patients but additional factors clearly contribute. The results suggest that patients who do and do not exhibit temporal processing deficits on behavioural tasks produce different patterns of reduction in duration mismatch negativity.     

Ketamine-induced deficits in auditory and visual context-dependent processing in healthy volunteers: implications for models of cognitive deficits in schizophrenia

BACKGROUND: In patients with schizophrenia, deficient generation of mismatch negativity (MMN)-an event-related potential (ERP) indexing auditory sensory ("echoic") memory-and a selective increase of "context dependent" ("BX") errors in the "A-X" version of the Continuous Performance Test (AX-CPT) indicate an impaired ability to form and use transient memory traces. Animal and human studies implicate deficient N-methyl-D-aspartate receptor (NMDAR) functioning in such abnormalities. In this study, effects of the NMDAR antagonists ketamine on MMN generation and AX-CPT performance were investigated in healthy volunteers to test the hypothesis that NMDARs are critically involved in human MMN generation, and to assess the nature of ketamine-induced deficits in AX-CPT performance. METHODS: In a single-blind placebo-controlled study, 20 healthy volunteers underwent an infusion with subanesthetic doses of ketamine. The MMN-to-pitch and MMN-to-duration deviants were obtained while subjects performed an AX-CPT. RESULTS: Ketamine significantly decreased the peak amplitudes of the MMN-to-pitch and MMN-to-duration deviants by 27% and 21%, respectively. It induced performance deficits in the AX-CPT characterized by decreased hit rates and specific increases of errors (BX errors), reflecting a failure to form and use transient memory traces of task relevant information. CONCLUSIONS: The NMDARs are critically involved in human MMN generation. Deficient MMN in schizophrenia thus suggests deficits in NMDAR-related neurotransmission. N-methyl-D-aspartate receptor dysfunction may also contribute to the impairment of patients with schizophrenia in forming and using transient memory traces in more complex tasks, such as the AX-CPT. Thus, NMDAR-related dysfunction may underlie deficits in transient memory at different levels of information processing in schizophrenia. Arch Gen Psychiatry. 2000;57:1139-1147.     

Concentrative meditation enhances preattentive processing: a mismatch negativity study

The mismatch negativity (MMN) paradigm that is an indicator of preattentive processing was used to study the effects of concentrative meditation. Sudarshan Kriya Yoga meditation is a yogic exercise practiced in an ordered sequence beginning with breathing exercises, and ending with concentrative (Sahaj Samadhi) meditation. Auditory MMN waveforms were recorded at the beginning and after each of these practices for meditators, and equivalently after relaxation sessions for the nonmeditators. Overall meditators were found to have larger MMN amplitudes than nonmeditators. The meditators also exhibited significantly increased MMN amplitudes immediately after meditation suggesting transient state changes owing to meditation. The results indicate that concentrative meditation practice enhances preattentive perceptual processes, enabling better change detection in auditory sensory memory.     

A stroke patient with impairment of auditory sensory (echoic) memory

A 42-year-old man suffered damage to the left supra-sylvian areas due to a stroke and presented with verbal short-term memory (STM) deficits. He occasionally could not recall even a single syllable that he had heard one second before. A study of mismatch negativity using magnetoencephalography suggested that the duration of auditory sensory (echoic) memory traces was reduced on the affected side of the brain. His maximum digit span was four with auditory presentation (equivalent to the 1st percentile for normal subjects), whereas it was up to six with visual presentation (almost within the normal range). He simply showed partial recall in the digit span task, and there was no self correction or incorrect reproduction. From these findings, reduced echoic memory was thought to have affected his verbal short-term retention. Thus, the impairment of verbal short-term memory observed in this patient was “pure auditory” unlike previously reported patients with deficits of the phonological short-term store (STS), which is the next higher-order memory system. We report this case to present physiological and behavioral data suggesting impaired short-term storage of verbal information, and to demonstrate the influence of deterioration of echoic memory on verbal STM.     

Mismatch negativity responses in schizophrenia: a combined fMRI and whole-head MEG study

OBJECTIVE: Mismatch negativity is an event-related brain response sensitive to deviations within a sequence of repetitive auditory stimuli. It is thought to reflect short-term sensory memory and is independent of higher-level cognitive processes. Mismatch negativity response is diminished in patients with schizophrenia. Little is known about the mechanisms of this decreased response, the contribution of the different hemispheres, and its locus of generation. METHOD: Patients with schizophrenia (N=12) and matched comparison subjects (N=12) were studied. A novel design to measure mismatch negativity responses to deviant auditory stimuli was generated by using the switching noises from the functional magnetic resonance imaging (fMRI) scanner, thus avoiding any interfering background sound. Stimuli included deviants of amplitude (9 dB lower) and duration (76 msec shorter) presented in a random sequence. The scanner noise was recorded and applied to the same subjects in a whole-head magnetoencephalography (MEG) device. Neuromagnetic and hemodynamic responses to the identical stimuli were compared between the patients and comparison subjects. RESULTS: As expected, neuromagnetic mismatch fields were smaller in the patient group. More specifically, a lateralization to the right for duration deviance was only found in comparison subjects. For the relative amplitude of the blood-oxygen-level-dependent signal (measured with fMRI), differences emerged in the secondary (planum temporale), but not primary (Heschl's gyrus), auditory cortex. Duration deviants achieved a right hemispheric advantage only in the comparison group. A significantly stronger lateralization to the left was found for the deviant amplitude stimuli in the patients. CONCLUSIONS: The data support the view of altered hemispheric interactions in the formation of the short-term memory traces necessary for the integration of auditory stimuli. This process is predominantly mediated by the planum temporale (secondary auditory cortex). Altered interaction of regions within the superior temporal plane and across hemispheres could be in part responsible for language-mediated cognitive (e.g., verbal memory) and psychopathological (hallucinations, formal thought disorder) symptoms in schizophrenia.     

Mismatch negativity evoked by the McGurk-MacDonald effect: a phonetic representation within short-term memory.

OBJECTIVES: The McGurk-MacDonald illusory percept is obtained by dubbing an incongruent articulatory movement on an auditory phoneme. This type of audiovisual speech perception contributes to the assessment of theories of speech perception. The mismatch negativity (MMN) reflects the detection of a deviant stimulus within the auditory short-term memory and besides an acoustic component, possesses, under certain conditions, a phonetic one. The present study assessed the existence of an MMN evoked by McGurk-MacDonald percepts elicited by audiovisual stimuli with constant auditory components. METHODS: Cortical evoked potentials were recorded using the oddball paradigm on 8 adults in 3 experimental conditions: auditory alone, visual alone and audiovisual stimulation. Obtaining illusory percepts was confirmed in an additional psychophysical condition. RESULTS: The auditory deviant syllables and the audiovisual incongruent syllables elicited a significant MMN at Fz. In the visual condition, no negativity was observed either at Fz, or at O(z). CONCLUSIONS: An MMN can be evoked by visual articulatory deviants, provided they are presented in a suitable auditory context leading to a phonetically significant interaction. The recording of an MMN elicited by illusory McGurk percepts suggests that audiovisual integration mechanisms in speech take place rather early during the perceptual processes.