Auditory stimuli mimicking ambient sounds drive temporal "delta-brushes" in premature infants

Abstract

In the premature infant, somatosensory and visual stimuli trigger an immature electroencephalographic (EEG) pattern, "delta-brushes," in the corresponding sensory cortical areas. Whether auditory stimuli evoke delta-brushes in the premature auditory cortex has not been reported. Here, responses to auditory stimuli were studied in 46 premature infants without neurologic risk aged 31 to 38 postmenstrual weeks (PMW) during routine EEG recording. Stimuli consisted of either low-volume technogenic "clicks" near the background noise level of the neonatal care unit, or a human voice at conversational sound level. Stimuli were administrated pseudo-randomly during quiet and active sleep. In another protocol, the cortical response to a composite stimulus ("click" and voice) was manually triggered during EEG hypoactive periods of quiet sleep. Cortical responses were analyzed by event detection, power frequency analysis and stimulus locked averaging. Before 34 PMW, both voice and "click" stimuli evoked cortical responses with similar frequency-power topographic characteristics, namely a temporal negative slow-wave and rapid oscillations similar to spontaneous delta-brushes. Responses to composite stimuli also showed a maximal frequency-power increase in temporal areas before 35 PMW. From 34 PMW the topography of responses in quiet sleep was different for "click" and voice stimuli: responses to "clicks" became diffuse but responses to voice remained limited to temporal areas. After the age of 35 PMW auditory evoked delta-brushes progressively disappeared and were replaced by a low amplitude response in the same location. Our data show that auditory stimuli mimicking ambient sounds efficiently evoke delta-brushes in temporal areas in the premature infant before 35 PMW. Along with findings in other sensory modalities (visual and somatosensory), these findings suggest that sensory driven delta-brushes represent a ubiquitous feature of the human sensory cortex during fetal stages and provide a potential test of functional cortical maturation during fetal development.

Figure 1. Auditory evoked delta-brushes by “click” and voice in temporal cortex.

A. Electroencephalogram (EEG) in a 31 postmenstrual week (PMW) premature infant during active sleep (AS) showing continuous activity with diffuse slow waves and multifocal delta-brushes (red stars). Traces are shown with mean reference montage (high-pass filter 0.53 Hz, notch filter 50 Hz, electrodes placement using 10/20 international system). ECG: electrocardiogram, RESP: respiration, B. Example of temporal delta-brushes evoked by single auditory voice stimulus, recorded during quiet sleep (QS) at 31 PMW. Corresponding wavelet analyses of T3-reference derivation is shown below (delta-brushes are outlined in blue on the T3-reference trace above). C. Example of temporal delta-brushes evoked by single auditory “click” stimulus recorded during QS at 31 PMW and corresponding wavelet analyses on T4-reference derivation. D. Representative example of occipital delta-brushes evoked by single visual flash stimulus, recorded during QS at 32 PMW with corresponding wavelet analysis on O2-reference derivation.

Figure 2. Age and sleep stage dependence of auditory evoked delta-brushes.

A–B: Left column: Increased delta-brush occurrence (expressed as a ratio of evoked to spontaneous brushes) for the 2 second period following “periodic” auditory stimulation (“click” or voice)/baseline rate. QS and AS are graphed separately. Left and right electrodes are pooled and each electrode pair is shown by different colors (error bar is SEM). Orange circles show significant elevation above baseline (p<0.05), while the blue asterisk shows significant difference between age groups. Right column: elevation of frequency power (1–50 Hz) for 32–34 postmenstrual weeks. QS and AS are graphed separately Colored line denotes mean elevation for each electrode, while SEM is indicated by shaded region. Solid bold lines show the frequencies significantly elevated above baseline (p<0.05); dotted lines show non-significant frequencies.

Figure 3. Developmental profile of auditory evoked responses.

Pooled averages from all premature infants quantifying developmental changes in the rapid oscillations of the delta-brush (‘brush’) (A–C) as well as the slow negative wave (‘delta’) (D–F). A. Topography of rapid oscillations (8–25 Hz) evoked by auditory stimulation at 31–34 postmenstrual weeks (PMW) shows a temporal dominance. Frequency power is summed in the relevant frequencies 2 s after stimulation and compared to before. B. The duration of evoked rapid oscillations is shown for the T3 (red) and T4 (blue) electrode for each premature according to PMW. Thick black line shows population mean. Thin lines show significant difference between age groups (p<0.05). C. As B but peak increase in frequency power is plotted. D. Topography of the mean evoked potential at the peak of the negative potential (860 ms) after stimulus for 31–34 PMW. Blue color shows temporal prominence of negative potential. E–F. Quantification of evoked negative slow wave for T3 (red) and T4 (blue) electrodes. Thick black line shows population mean. Thin lines show significant difference between age groups (p<0.05). The summed negative potential in the 2 s following stimulation (‘Total charge flux’, E) and the peak amplitude of the negative potential (‘Maximum Amplitude’, F) are also shown.

Figure 4. Power spectrum changes after auditory stimuli (click, voice and composite) and visual stimuli (flash) in quiet sleep according to age and EEG frequency bands. AB.

Power spectrum increase after auditory stimuli “click” (A) and voice (B), for each electrode and in each frequency band. Graphs are shown for 3 age groups in postmenstrual weeks (PMW): <34 (above), 34–35 (middle) and >35 (below). At 32–33 PMW, click induces evoked responses on T3, T4, T5, T6, CZ electrodes whereas voice induces a response only on T4 and T3 (p<0.01) but the difference is not significant, (interaction test, all p-values >0.01). At 34–35 PMW, all electrodes record a response to “click” (p<0.01), but voice induces a response only on T4 (p<0.01) (interaction test, p<0.01). At 36–37 PMW, “click” induces a response at FP1, FP2, C4, O1, T4, T6 electrodes but voice induces a response only on T4 (p<0.01). C. Power spectrum increase after auditory composite stimuli in “triggered” population. The increase is statistically significant on all electrodes in all age groups (p<0. 01). At 31–33 PMW the response is greater on mid temporal T3 and T4 electrodes than on the other electrodes. D. Power spectrum increase after visual stimuli. Visual stimulation evoke maximal occipital power spectrum increase at 31–33 PMW (p<0.01).