Toward an electrocortical biomarker of cognition for newborn infants

Abstract

The event-related potential (ERP) effect of mismatch negativity (MMN) was the first electrophysiological probe to evaluate cognitive processing (change detection) in newborn infants. Initial studies of MMN predicted clinical utility for this measure in identification of infants at risk for developmental cognitive deficits. These predictions have not been realized. We hypothesized that in sleeping newborn infants, measures derived from wavelet assessment of power in the MMN paradigm would be more robust markers of the brain's response to stimulus change than the ERP-derived MMN. Consistent with this premise, we found increased power in response to unpredictable and infrequent tones compared to frequent tones. These increases were present at multiple locations on the scalp over a range of latencies and frequencies and occurred even in the absence of an ERP-derived MMN. There were two predominant effects. First, theta band power was elevated at middle and late latencies (200 to 600 ms), suggesting that neocortical theta rhythms that subserve working memory in adults are present at birth. Second, late latency (500 ms) increased power to the unpredictable and infrequent tones was observed in the beta and gamma bands, suggesting that oscillations involved in adult cognition are also present in the neonate. These findings support the expectation that frequency dependent measures, such as wavelet power, will improve the prospects for a clinically useful test of cortical function early in the postnatal period.

Figure 1

A. Mean over all electrodes of log power difference (response to infrequent minus response to frequent tones) shown by color, with red denoting greater positive difference (i.e. log power higher for infrequent than frequent tones) and blue denoting greater negative difference (i.e. log power higher for frequent tones). In A, significant differences are shown with full transparency and contours are drawn for p = 0.05 and 0.01 (solid and dashed, respectively). P-values are shown in B.

Figure 1

A. Mean over all electrodes of log power difference (response to infrequent minus response to frequent tones) shown by color, with red denoting greater positive difference (i.e. log power higher for infrequent than frequent tones) and blue denoting greater negative difference (i.e. log power higher for frequent tones). In A, significant differences are shown with full transparency and contours are drawn for p = 0.05 and 0.01 (solid and dashed, respectively). P-values are shown in B.

Figure 2

A. Mean over time-frequency areas of log power difference (response to infrequent tones minus response to frequent tones) at each electrode, shown in topography plots that are planar projections of electrode locations (nose at the top). The time-frequency areas have a frequency width that varies as log 2 times the center frequency and a temporal width fixed at 100 ms, with 50% overlap. In A, difference in log power is shown with the same color scale as Figure 1A and significant differences (p < 0.05) are shown with larger ball size. P-values are shown in B.

Figure 2

A. Mean over time-frequency areas of log power difference (response to infrequent tones minus response to frequent tones) at each electrode, shown in topography plots that are planar projections of electrode locations (nose at the top). The time-frequency areas have a frequency width that varies as log 2 times the center frequency and a temporal width fixed at 100 ms, with 50% overlap. In A, difference in log power is shown with the same color scale as Figure 1A and significant differences (p < 0.05) are shown with larger ball size. P-values are shown in B.

Figure 3

Topography of the MMN (infrequent tone ERP minus frequent), shown in a planar projection of electrode locations with nose at the top. ERPs used an averaged-mastoids reference. Time axes are from -100 ms to 768 ms relative to stimulus onset. Vertical lines at t = 0 extend from -1 to +1 microvolt. Red asterisks denote time points where the difference was significant (p < 0.05). A significant difference at mid-latencies below 450 ms only occurred at one left central Electrode.

Figure 4

Top panels: Group mean (+/- standard error) ERPs for the frequent (blue) and infrequent (red) tones referenced to averaged-mastoids for six electrode locations of the International 10-20 system. Asterisks denote time points where the difference between ERPs reached significance (p < 0.05). Middle panels: Same as top panels except using average reference. Bottom panels: Differences in log power (infrequent minus frequent) at the same locations over both time and frequency in the same format as Figure 1A. Significant differences are highlighted using contour lines of p-values (solid p = 0.05, dashed p = 0.01) and full transparency of the color scale. Note the absence of an MMN effect (i.e. any significant difference at middle latencies) in the upper two rows in contrast to many significant wavelet power effects in the third row.

Figure 5

Histograms of individual subject results for mid-late latency theta power, late latency beta and late latency gamma power at the electrode location where they were most significant.