Spatiotemporal maturation of the central and lateral N1 components to tones.

This paper examines maturational changes in the spatiotemporal features of central and lateral N1 components of the auditory evoked potentials (AEPs) to tone stimuli presented with a long stimulus onset asyncrony (SOA; 4200 ms) using the scalp current density (SCD) technique. A group of typically developing children ranging from 6 to 12 years of age and a group of adults were studied. Recently studies have begun to explore the topography of these components in children. These studies, however, often used rapidly presented stimuli and did not elicit observable central N1s in the younger children. Our stimuli elicited both central and lateral N1s. Peak latencies of both components decreased with age. Peak amplitude also decreased with age for the lateral N1 but not for the central N1. Consequently, the difference between the lateral N1 and the central N1 amplitudes (or the ratio of lateral N1 amplitude to central N1 amplitude) also decreased with age, dramatically altering the morphology of the elicited AEP waveforms. Topography of the lateral N1 did not change with age. The location of maximal activation for the central N1 appeared to move more medially with age but this 'apparent' movement is probably due to the decreasing impact of the partially overlapping lateral N1 component whose amplitude is significantly smaller in adults than in children.

Neurophysiological indices of language impairment in children.

Recent investigations of children with specific language impairment (SLI) have found deviant anatomical asymmetry of the perisylvian cortex. These studies argue that this deviant anatomical asymmetry is linked to the language disorders of SLI children. To date no studies have examined whether deviant functional asymmetry underlies the processing of spoken language in these children. In the current study, brain-electrical activity was recorded from 31 scalp sites while children with SLI listened to auditorally presented stories and two different nonsense contexts. Electrical activity was time-locked to the grammatical word "the" in these contexts. The SLI children showed reversed asymmetry compared to control children from 200 ms to 400 ms in processing "the" in all contexts. More specifically, they showed depressed processing at the left temporal scalp site (T7) and enhanced processing at the right temporal site (T8). The second spatial derivative (the Laplacian) of the voltage activity was calculated to remove constant voltage potential and uniform changes in voltage potential across the scalp. The Laplacian analysis indicated that the sources of the positive electrical activity seen at the temporal electrode sites T7 and T8 are the lateral surfaces of the temporal cortices. A comparison of the scalp topography of the voltage potentials and Laplacian also suggests that children with SLI lack some contribution from a deep neural generator, possibly in the hippocampus or basal ganglia. This investigation is the first to demonstrate a direct link between deviant neurophysiological asymmetry and the processing of spoken language in children with SLI.

Mismatch negativity in children and adults, and effects of an attended task.

Attention has been shown to modulate the amplitude of the mismatch negativity (MMN) elicited by a small deviation in auditory stimuli in adults. The present study examined the effects of attention and deviant size on MMN amplitude in children. Children and adults were presented with sequences of tones containing standards (1000 Hz) and three deviants varying in degree of deviance from the standard (1050, 1200, and 1500 Hz). Tones were presented in three conditions: (1) while participants ignored them; (2) while participants listened to them and responded to all three deviants; and (3) while participants again ignored them. We found that the MMNs elicited by the hard deviant (1050 Hz) were larger when the children were actively discriminating the stimuli than when they were ignoring them. However, the MMNs elicited by the easy and medium deviants (1500 and 1200 Hz, respectively) in the children and by all three deviants in the adults were not affected by attention.

Deviant neurophysiological asymmetry in children with language impairment.

Deviant anatomical asymmetry of perisylvian cortex is argued to be linked to specific language impairment (SLI). However, no studies have examined whether deviant functional asymmetry underlies the processing of spoken language. In the current study, brain-electrical activity was recorded from 31 scalp sites to the function word 'the' embedded in auditorally presented stories and nonsense contexts. The SLI children showed reversed asymmetry at electrode sites over temporal cortex compared to control children in processing this word in all contexts. They also appear to lack some contribution from a deep neural generator in processing 'the' in the story. This investigation is the first to demonstrate a direct link between deviant neurophysiological asymmetry and the processing of spoken language in children with SLI.

Maturation of mismatch negativity in school-age children.

OBJECTIVE: Event-related potentials were recorded to investigate the maturation of auditory processing in school-age children. DESIGN: The mismatch negativity (MMN) was obtained in an oddball tone discrimination paradigm in 66 school-age children and 12 adults. In the children's data, a prominent negativity to both the standard and deviant tone, peaking around 200 msec, was observed, and compared with the N1 auditory evoked potential component. RESULTS: The MMN was found to decrease with latency by 11 msec/yr from 4 to 10 yr of age. No developmental change in MMN amplitude was seen from 4 to 10 yr of age. However, the MMN amplitude was significantly smaller in adults than in children. The prominent negativity in children was significantly later than the adult N1 component, and did not change in latency from 4 to 10 yr of age. This finding adds to a body of evidence suggesting that this prominent negativity and the adult N1 are not the same component. The magnitude of the prominent negativity in children decreased slightly with age. CONCLUSION: Changes in the timing of the brain discriminative response, MMN, suggest systematic maturational changes in auditory processing.

The effects of decreased audibility produced by high-pass noise masking on N1 and the mismatch negativity to speech sounds /ba/and/da.

This study investigated the effects of decreased audibility produced by high-pass noise masking on the cortical event-related potentials (ERPs) N1 and mismatch negativity (MMN) to the speech sounds /ba/ and /da/, presented at 65 dB SPL. ERPs were recorded while normal listeners (N = 11) ignored the stimuli and read a book. Broadband masking noise was simultaneously presented at an intensity sufficient to mask the response to the speech sounds, and subsequently high-pass filtered. The conditions were QUIET (no noise); high-pass cutoff frequencies of 4000, 2000, 1000, 500, and 250 Hz; and broadband noise. Behavioral measures of discrimination of the speech sounds (d' and reaction time) were obtained separately from the ERPs for each listener and condition. As the cutoff frequency of the high-pass masker was lowered, ERP latencies increased and amplitudes decreased. The cutoff frequency where changes first occurred differed for N1 and MMN. N1 showed small systematic changes across frequency beginning with the 4000-Hz high-pass noise. MMN and behavioral measures showed large changes that occurred at approximately 1000 Hz. These results indicate that decreased audibility, resulting from the masking, affects N1 and the MMN in a differential manner. N1 reflects the presence of audible stimulus energy, being present in all conditions where stimuli were audible, whether or not they were discriminable. The MMN is present only for those conditions where stimuli were behaviorally discriminable. These studies of cortical ERPs in high-pass noise studies provide insight into the changes in brain processes and behavioral performance that occur when audibility is reduced, as in hearing loss.

Electrophysiological evidence of developmental changes in the duration of auditory sensory memory.

In behavioral studies, children's memory for tonal frequency has been found to persist for less time than adults' (T. A. Keller & N. Cowan, 1994). The present study was done to evaluate the argument that this effect is due to changes in auditory sensory memory and not to attentional mechanisms. This question was investigated using mismatch negativity (MMN), an auditory event-related potential considered to be insensitive to attention. Participants were 6-7-, 8-10-, and 11-12-year-old children and adults. They were presented with trains of stimuli, beginning with either a standard (1000 Hz) or a deviant (1200 Hz) tone with trains separated by either 1 s or 8 s. All 4 groups exhibited MMNs after delays of 1 s, but only the adults and oldest children exhibited MMNs after 8 s, indicating that there are maturational changes in the duration of auditory sensory memory.

The effects of decreased audibility produced by high-pass noise masking on cortical event-related potentials to speech sounds/ba/and/da.

This study investigated the effects of decreased audibility produced by high-pass noise masking on cortical event-related potentials (ERPs) N1, N2, and P3 to the speech sounds /ba/and/da/presented at 65 and 80 dB SPL. Normal-hearing subjects pressed a button in response to the deviant sound in an oddball paradigm. Broadband masking noise was presented at an intensity sufficient to completely mask the response to the 65-dB SPL speech sounds, and subsequently high-pass filtered at 4000, 2000, 1000, 500, and 250 Hz. With high-pass masking noise, pure-tone behavioral thresholds increased by an average of 38 dB at the high-pass cutoff and by 50 dB one octave above the cutoff frequency. Results show that as the cutoff frequency of the high-pass masker was lowered, ERP latencies to speech sounds increased and amplitudes decreased. The cutoff frequency where these changes first occurred and the rate of the change differed for N1 compared to N2, P3, and the behavioral measures. N1 showed gradual changes as the masker cutoff frequency was lowered. N2, P3, and behavioral measures showed marked changes below a masker cutoff of 2000 Hz. These results indicate that the decreased audibility resulting from the noise masking affects the various ERP components in a differential manner. N1 is related to the presence of audible stimulus energy, being present whether audible stimuli are discriminable or not. In contrast, N2 and P3 were absent when the stimuli were audible but not discriminable (i.e., when the second formant transitions were masked), reflecting stimulus discrimination. These data have implications regarding the effects of decreased audibility on cortical processing of speech sounds and for the study of cortical ERPs in populations with hearing impairment.

Electrophysiologic manifestations of impaired temporal lobe auditory processing in verbal auditory agnosia.

The present study examined the extent to which verbal auditory agnosia (VAA) is primarily a phonemic decoding disorder, as contrasted to a more global defect in acoustic processing. Subjects were six young adults who presented with VAA in childhood and who, at the time of testing, showed varying degrees of residual auditory discrimination impairment. They were compared to a group of young adults with normal language development matched for age and gender. Cortical event-related potentials (ERPs) were recorded to tones and to consonant-vowel stimuli presented in an "oddball" discrimination paradigm. In addition to cortical ERPs, auditory brainstem responses (ABRs) and middle latency responses (MLRs) were recorded. Cognitive and language assessments were obtained for the VAA subjects. ABRs and MLRs were normal. In comparison with the control group, the cortical ERPs of the VAA subjects showed a delay in the N1 component recorded over lateral temporal cortex both to tones and to speech sounds, despite an N1 of normal latency overlying the frontocentral region of the scalp. These electrophysiologic findings indicate a slowing of processing of both speech and nonspeech auditory stimuli and suggest that the locus of this abnormality is within the secondary auditory cortex in the lateral surface of the temporal lobes.

Relations between infant neurobehavioral performance and cognitive outcome in very low birth weight preterm infants.

The predictive utility of three aspects of neonatal neurobehavioral performance was examined in 144 very low birth weight (< 1500 g) preterms who were followed until 6 years of age. Visual-following and auditory-orienting composites derived from the Einstein Neonatal Neurobehavioral Assessment Scale were modestly related to the Mental Developmental Index (MDI) and IQ scores at several ages, whereas the active motility composite was only related to MDI scores at 1 year of age (corrected). Infants who showed deviant performance on both visual following and auditory orienting composites had significantly lower cognitive test scores at 1 and 6 years of age and were more likely to be classified as subaverage at 6 years of age (IQ < 85). Group differences were independent of both neonatal health status and motor scores and were not due to the performance of children with severe sensory impairments. These findings suggest that visual following and auditory orienting measured in the neonatal period can offer a useful way of indexing initial capacities.

Developmental studies and clinical application of mismatch negativity: problems and prospects.

There is wide interest in the clinical application of mismatch negativity (MMN) to assess discriminative capabilities in individuals whose auditory capacities are difficult to determine, including infants, young children and those with severe cognitive impairment. Before MMN can be used as a clinical electrophysiologic measure, it is necessary to establish that it can be reliably elicited in normal individuals. This chapter describes a detailed analysis of MMN recorded in a group of healthy 8-yr-old children to assess intrasubject and intersubject reliability of the response. We conclude that although statistically reliable results can be obtained with group data, and perhaps even in individuals when large numbers of stimuli can be delivered, the unfavorable signal to noise ratio of individual MMN data currently limits its clinical applicability. Suggestions for approaches to surmount these difficulties are presented for its eventual clinical usefulness.

Endogenous event-related potentials as indices of dementia in multiple sclerosis patients.

Auditory event-related potentials (ERPs) were recorded in a "double oddball" paradigm requiring an easy and a hard pitch discrimination from multiple sclerosis (MS) patients with and without dementia, and a group of age and sex matched normal subjects. Cognitive function was assessed by a short battery of neuropsychologic (NP) tests, and the two groups of MS patients were selected on the basis of substantial non-overlapping degrees of cognitive deficit in the demented as compared to the non-demented group. The N100, P200 and P300 ERP components were longer in latency in the demented patients, and the N100-P300 interval was prolonged as well, compared to the non-demented patients, whose ERP latencies did not differ from those of the normal subjects. Increased P300 latency was associated with poorer performance on the NP tests, especially those sensitive to impairment of learning and retrieval from memory. The reaction times of both patient groups were prolonged as compared to the controls, whereas the accuracy of the demented patients was significantly poorer than that of the non-demented patients.

Flash and pattern-reversal visual evoked potential abnormalities in infants and children with cerebral blindness.

Visual evoked potentials (VEPs) were recorded of 60 infants and children with cerebral blindness, aged between six weeks and 10 years, and compared with age-matched normative data. Every patient had abnormal VEPs. 18 had absent flash and pattern VEPs and 13 had atypical or atypical and asymmetrical flash and pattern VEPs. Of the remaining 29, most had greater abnormality of pattern than of flash VEPs and greater abnormalities over parietal and temporal than occipital areas. Eight patients had normal occipital responses to flash and five others had delayed responses with normal morphology. One had normal occipital responses to pattern stimuli. All of these had abnormal late occipital responses or abnormal responses over the parietal and temporal areas. It is recommended that visual assessments using VEPs employ both flash and pattern stimuli, that pre-occipital as well as occipital recordings be made and that tracings be compared with age-specific normative data.

Evoked potential assessment of auditory system integrity in infants.

One child in 750 is born with a handicapping hearing impairment. The methods available to screen and evaluate infants at risk (auditory brainstem responses, middle latency responses, and cortical auditory evoked potentials) are reviewed, explained, and illustrated with case histories.

Cortical responses to speech sounds and their formants in normal infants: maturational sequence and spatiotemporal analysis.

Cortical auditory evoked potentials (AEPs) to the synthesized syllables [da[ and [ta[ and to the isolated 3 formants of [da[ were obtained from 32 normal infants studied at monthly intervals from birth through 3 months and at 6 months of age. A bilateral array of 16 electrodes referenced to the mid-occiput permitted a topographic analysis of the cortical AEPs at selected latencies. A differential maturational sequence was seen: a predominantly negative cortical AEP wave form became positive, first over the frontocentral region (around term), and then over the temporal region (at 1-2 months). The timing of these electrophysiological changes coincides with a differential anatomical maturational sequence in the auditory cortex, as myelination and synaptogenesis are more advanced in primary than secondary auditory areas at term. All infants in this study followed this developmental sequence. However, there was no systematic effect of the center frequency of the formant stimuli on the maturational level of their respective cortical AEPs, suggesting a relative maturational equivalence in those regions of auditory cortex responding to stimuli across the frequency range present in human speech. In term infants, an initial midline positivity and bitemporal negativities were asynchronous in their peak and offset latencies. suggesting independent generators for each of these components. In infants from 3 to 6 months of age, cortical AEP wave forms consisted of 2 initial positive peaks followed by a negative peak. While the wave forms were similar over midline and lateral scalp, spatiotemporal analysis revealed differences in the latency of onset, duration and in the spatial extent of these components, again suggesting that 2 bilateral, temporally overlapping generators contribute to the cortical AEP. No systematic topographic difference was observed in the cortical AEPs elicited by each of the 3 formants, which differed in center frequencies.

Progressive multifocal leukoencephalopathy of the posterior fossa in an AIDS patient: clinical, radiographic and evoked potential findings.

A 39-year-old intravenous drug user presented with dysarthria and a syndrome of the left cerebellar hemisphere. While in hospital, he developed progressive brainstem findings. Repeated CT scans revealed a lucency in the white matter of the left cerebellar hemisphere. Brainstem auditory and short-latency somatosensory evoked potentials provided evidence of brainstem dysfunction without corresponding lesions on CT. Biopsy of the cerebellum established the diagnosis of progressive multifocal leukoencephalopathy (PML) and the acquired immunodeficiency syndrome (AIDS). Postmortem examination revealed brainstem lesions appropriate to the evoked potential findings and a radiographically inapparent lesion in the right internal capsule. Based on this case and a review of the literature we conclude that: (1) PML occurs with significant prevalence in AIDS patients and may involve the posterior fossa; (2) the diagnosis of posterior fossa PML is suggested by certain clinical and radiographic criteria and may be confirmed by brain biopsy; (3) evoked potentials may be abnormal in PML and can reveal functional abnormalities of white matter without apparent CT abnormalities.

The utility of visual evoked potentials using hemifield stimulation and several check sizes in the evaluation of suspected multiple sclerosis.

One hundred and eleven patients with suspected multiple sclerosis (64 possible, 47 probable) and 16 with a definite diagnosis of MS were evaluated with pattern-reversal visual evoked potentials (VEPs), employing monocular full-field checks subtending 7', 14' and 28' of visual angle, and right and left hemifield 28' checks. Thirty-seven patients (29%) had a completely normal study. Sixty-six patients (52%) had abnormal responses to full-field 28' checks, and in 13 (10%) of these, additional abnormalities were found in one or more of the other test conditions, which indicated the presence of an additional site of dysfunction in the visual pathway. Twenty-four patients (19%) with 'normal' full-field 28' responses had abnormalities in one or more of the other test conditions; these included prolonged latency to small size (7' and 14') full-field checks, abnormal responses in homonymous hemifields, and abnormal responses limited to a hemifield of one eye. Thus, the use of several check sizes and hemifield stimulation not only increases the sensitivity of VEPs in the evaluation of patients with suspected demyelinating disease, but enhances the capability of the VEP to demonstrate more than one area of visual system impairment.

Electrophysiologic assessment of auditory pathways in high risk infants.

This study evaluated auditory processing in a group of 59 infants at risk for subsequent hearing and language disorders due to low birthweight and/or perinatal asphyxia. Auditory system integrity was evaluated electrophysiologically by recording the auditory brainstem response (ABR), middle latency response (MLR) and the cortical auditory evoked potential (CAEP). 63% of the babies had normal peripheral function or slight unilateral impairment; 84% had normal brainstem auditory system function; 82% showed normal MLRs; and 81% showed normal CAEPs. Fifty-three percent of the babies were normal on all tests and only 3% were deviant on all tests. The remaining infants showed diverse patterns of peripheral, brainstem and cortical abnormalities.

Trimodal evoked potentials compared with magnetic resonance imaging in the diagnosis of multiple sclerosis.

Twenty-three patients with the clinical diagnosis of possible multiple sclerosis (MS) were tested with magnetic resonance imaging (MRI) and trimodal evoked potentials. Fourteen patients showed abnormalities on both MRI scans and at least one evoked potential modality (65%). Four patients had normal MRI scans but at least one abnormality on evoked potential testing (17%). One patient had normal triple evoked potentials with an abnormal MRI result. Four patients had normal results on both MRI and triple evoked potential testing; two of these patients were later found to have immunologic abnormalities in the cerebrospinal fluid consistent with the diagnosis of MS. Combined evoked potential testing was found to have a higher sensitivity than MRI in confirming a diagnosis of MS. Three patients with the clinical diagnosis of definite MS were also tested. All these patients showed abnormalities on evoked potential testing, although one patient had a normal MRI result. Of all 26 patients who were studied, 17 showed abnormal MRI results and 21 showed at least one abnormality on evoked potential testing.

Neurological complications in infants and children with acquired immune deficiency syndrome.

Neurological complications occurred in 6 children, aged 6 months to 5 years, with acquired immune deficiency syndrome who were followed for 14 months. The most frequent manifestations included encephalopathies, acquired microcephaly, and pyramidal tract signs. Computed tomographic examinations showed variable degrees of cortical atrophy with ventricular dilatation and calcification. Electrophysiological abnormalities were demonstrated. Two children had documented central nervous system infections. Neurological deterioration resulted in dementia in 3 children. Cognitive impairment and developmental delays were evident in the other 3. Postmortem examination of the 3 children who died showed subacute cytomegalovirus encephalitis in 1; nonspecific hemispheric white matter changes, calcific vasopathy of the basal ganglia, and striking bilateral corticospinal tract degeneration in the second; and extensive calcific vasopathy of the basal ganglia and frontal centrum semiovale, and bilateral attenuation of the frontopontine and corticospinal tracts in the third.