The current study assessed the normal development of cortical auditory evoked potentials (CAEPs) in humans presented with pure tone stimuli at relatively fast stimulus rates. Traditionally, maturation of sound processing indexed by CAEPs has been studied in paradigms using inter-stimulus intervals (ISIs) generally slower than 1 Hz. While long ISIs may enhance the amplitude of CAEP components, speech information generally occurs at more rapid rates. These slower rates of sound presentation may not accurately assess auditory cortical functions in more realistic sound environments. We examined the effect of temporal rate on the elicitation of the P1-N1-P2-N2 components to unattended sounds at four levels of stimulus onset asynchrony (SOA, onset to onset, 200, 400, 600, and 800 ms) in children grouped separately by year (ages 8, 9, 10, 11 years), in adolescents (age 16 years) and in one group of young adults (ages 22-40 years). We found that both age and stimulus rate produced profound changes in CAEP morphology. Between the ages of 8-11 years, the P1 and N2 components dominated the ERP waveform at all stimulus rates. N1, the dominant CAEP component in adults, appeared as a bifurcation in a broad positive peak at earlier ages, and did not emerge as a separate component until adolescence. While the P1-N1-P2 components are more "adult-like" than "child-like" in the adolescent subjects, the N2 component, a hallmark of the child obligatory response, was still present. Faster rates resulted in the suppression of discrete components such that by 200 ms, only P1 in the adults and adolescents, and both P1 and N2 in the youngest children were discernable. We conclude that both age and ISI are important variables in the assessment of auditory cortex function and maturation. The presence of N2 in adolescents indicates that auditory cortical maturation persists into teen years.

Distractibility was investigated in three age groups of children (8-9, 10-11, and 12-13 years) with event-related brain potentials (ERPs) and performance measures in a forced-choice visual task. Distraction was reflected by increased reaction times (RTs) and decreased performance accuracy in the visual discrimination task following presentation of unexpected novel sounds. The amplitude of the late portion of the P3a elicited by novel sounds was largest for the youngest group and showed a centrally dominant scalp distribution and smallest for the oldest group with a frontal scalp distribution. A frontally dominant late negativity (LN) that was largest in the youngest group followed the P3a. Correlation between the RT increase caused by the distracting novel sounds and the amplitude of the LN elicited by these sounds suggested that the LN is associated with the degree of attention engaged by the distracting sounds.

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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.

SUMMARYPurpose: This study examines whether magnetoencephalographic (MEG) coherence imaging is more sensitive than the standard single equivalent dipole (ECD) model in lateralizing the site of epileptogenicity in patients with drug-resistant temporal lobe epilepsy (TLE). Methods: An archival review of ECD MEG analyses of 30 presurgical patients with TLE was undertaken with data extracted subsequently for coherence analysis by a blinded reviewer for comparison of accuracy of lateralization. Postoperative outcome was assessed by Engel classification. MEG coherence images were generated from 10 min of spontaneous brain activity and compared to surgically resected brain areas outlined on each subject's magnetic resonance image (MRI). Coherence values were averaged independently for each hemisphere to ascertain the laterality of the epileptic network. Reliability between runs was established by calculating the correlation between epochs. Match rates compared the results of each of the two MEG analyses with optimal postoperative outcome.Key Findings: The ECD method provided an overall match rate of 50% (13/16 cases) for Engel class I outcomes, with 37% (11/30 cases) found to be indeterminate (i.e., no spikes identified on MEG). Coherence analysis provided an overall match rate of 77% (20/26 cases). Of 19 cases without evidence of mesial temporal sclerosis, coherence analysis correctly lateralized the side of TLE in 11 cases (58%). Sensitivity of the ECD method was 41% (indeterminate cases included) and that of the coherence method 73%, with a positive predictive value of 70% for an Engel class Ia outcome. Intrasubject coherence imaging reliability was consistent from run-to-run (correlation >0.90) using three 10-min epochs. Significance: MEG coherence analysis has greater sensitivity than the ECD method for lateralizing TLE and demonstrates reliable stability from run-to-run. It, therefore, improves upon the capability of MEG in providing further information of use in clinical decisionmaking where the laterality of TLE is questioned.

Most night workers are unable to adjust their circadian rhythms to the atypical hours of sleep and wake. Between 10% and 30% of shiftworkers report symptoms of excessive sleepiness and/or insomnia consistent with a diagnosis of shift work disorder (SWD). Difficulties in attaining appropriate shifts in circadian phase, in response to night work, may explain why some individuals develop SWD. In the present study, it was hypothesized that disturbances of sleep and wakefulness in shiftworkers are related to the degree of mismatch between their endogenous circadian rhythms and the night-work schedule of sleep during the day and wake activities at night. Five asymptomatic night workers (ANWs) (3 females; [mean ± SD] age: 39.2 ± 12.5 yrs; mean yrs on shift = 9.3) and five night workers meeting diagnostic criteria (International Classification of Sleep Disorders [ICSD]-2) for SWD (3 females; age: 35.6 ± 8.6 yrs; mean years on shift = 8.4) participated. All participants were admitted to the sleep center at 16:00 h, where they stayed in a dim light (<10 lux) private room for the study period of 25 consecutive hours. Saliva samples for melatonin assessment were collected at 30-min intervals. Circadian phase was determined from circadian rhythms of salivary melatonin onset (dim light melatonin onset, DLMO) calculated for each individual melatonin profile. Objective sleepiness was assessed using the multiple sleep latency test (MSLT; 13 trials, 2-h intervals starting at 17:00 h). A Mann-Whitney U test was used for evaluation of differences between groups. The DLMO in ANW group was 04:42 ± 3.25 h, whereas in the SWD group it was 20:42 ± 2.21 h (z = 2.4; p < .05). Sleep did not differ between groups, except the SWD group showed an earlier bedtime on off days from work relative to that in ANW group. The MSLT corresponding to night work time (01:00-09:00 h) was significantly shorter (3.6 ± .90 min: [M ± SEM]) in the SWD group compared with that in ANW group (6.8 ± .93 min). DLMO was significantly correlated with insomnia severity (r = -.68; p < .03), indicating that the workers with more severe insomnia symptoms had an earlier timing of DLMO. Finally, SWD subjects were exposed to more morning light (between 05:00 and 11:00 h) as than ANW ones (798 vs. 180 lux [M ± SD], respectively z = -1.7; p < .05). These data provide evidence of an internal physiological delay of the circadian pacemaker in asymptomatic night-shift workers. In contrast, individuals with SWD maintain a circadian phase position similar to day workers, leading to a mismatch/conflict between their endogenous rhythms and their sleep-wake schedule.

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