Article Figures & Data
Figures
- Figure 1.
A, B, NIRS optode and EEG electrode locations (A) and NIRS sensitivity maps (B). A, NIRS optode (black) and EEG electrode (blue circles) locations are presented on a schematic of the top view of the head (left). The EEG reference electrode was placed at FCz (gray circle). The NIRS emitter and detector were placed in a holder (pictured right) at a fixed distance of 4 cm, with the emitter toward the front of the head (red dot in schematic). B, The sensitivity map of the optodes is shown at C1 (halfway between Cz and C3) in 2-mm-thick sagittal (left) and coronal (right) slices taken from a head model of 40-week-old infants. The scale bar indicates the log of the normalized sensitivity (in arbitrary units). A high sensitivity indicates that many photons pass through the given region on their way to a detector. Red and black arrows indicate the emitter and detector locations. A, Anterior; P, posterior; L, left; R, right; ECT, extracerebral tissue; CSF, cerebrospinal fluid; GM, gray matter; WM, white matter.
- Figure 2.
HbO2 GOF values and EEG N3P3 waveform PC weights correlate with peak Δ[HbO2] and N3P3 amplitudes, respectively, in term infants having a noxious heel lance. A, HRF used for classifying trials according to the presence of an HbO2 response. B, The PC used for classifying trials according to the presence of the nociceptive-specific N3P3 waveform is shown in bold, overlaid onto the average EEG response for clarity. C, NIRS HbO2 GOF values are plotted against peak positive [HbO2] changes, indicating a positive correlation that is almost significant (Spearman’s ρ = 0.51, p = 0.052, n = 15). D, EEG N3P3 waveform PC weights are plotted against the N3P3 amplitudes, indicating a significant positive correlation (Spearman’s ρ = 0.81, p = 0.0002, n = 16).
- Figure 3.
A, B, Nociceptive-specific responses can be identified in the average of NIRS (A) and EEG (B) trials classified as response present, but not in the average of those trials classified as response absent. A, Average (±SD) Δ[HbO2] following noxious heel lance (t = 0 s) at the contralateral primary somatosensory cortex in 10 response-present (left) and 5 response-absent (right) trials. B, Average (±SD) ERP at Cz following noxious heel lance (t = 0 ms) in nine response-present (left) and 7 response-absent (right) trials, with topography maps at the N and P peaks. Gray arrows indicate the location of the first waveform. Time points that are significantly different from baseline are highlighted in gray.
- Figure 4.
Average (±SD) hemodynamic response to a noxious heel lance (t = 0 s) at the contralateral primary somatosensory cortex in 15 term infants. [HbT], [HbO2], and [HHb] changes are plotted separately (in green, red, and blue, respectively), and time points that are significantly different from baseline are highlighted in gray.
- Figure 5.
Noxious stimulation elicits a more pronounced hemodynamic response than innocuous control or touch stimulation. A, Average (±SD) hemodynamic response to non-noxious control (left, n = 18 infants) and touch (right, n = 131 touches from 16 infants) at the contralateral primary somatosensory cortex. B, Results of an independent-samples t test comparing lance (black traces; n = 15 infants) and control (left) or touch (right). Average (±SD) [HbT], [HbO2], and [HHb] changes are plotted separately (in green, red, and blue, respectively), and statistically significant differences from baseline (A) or between stimuli (B) are highlighted in gray.
- Figure 6.
Average (±SD) EEG response at Cz following noxious heel lance (t = 0 ms) in 16 term infants when aligned to the first waveform (between 50 and 400 ms; left) and to the second waveform (between 350 and 600 ms; right), with topography maps at the N and P peaks. Time points between 50 and 300 ms (left) and between 350 and 600 ms (right) that are significantly different from baseline are highlighted in gray. Note that the group average responses are from the same group of infants but look different because the individual trials have been aligned differently. Gray arrows indicate the location of the second waveform when traces are aligned to waveform 1 (left) and of the first waveform when traces are aligned to waveform 2 (right).
- Figure 7.
Average (±SD) EEG response at Cz following innocuous control (left; n = 16 term infants) and touch (right; n = 11 term infants having 106 touch trials) stimulation when aligned to the N2P2 waveform (between 50 and 300 ms), with topography maps at the N and P peaks. Time points between 50 and 300 ms that are significantly different from baseline are highlighted in gray.
- Figure 8.
Combined EEG and NIRS recordings can be successfully performed in neonates in response to cutaneous stimulation. Simultaneous EEG (left) and NIRS (right) recordings in a single term infant following noxious heel lance (top) and innocuous control stimulation (bottom; stimulus at t = 0 s), showing artifact-free EEG traces at Cz and NIRS traces at C1. Arrows indicate the presence of a nociceptive-specific EEG waveform (red) following heel lance and an earlier EEG waveform (green) following both stimuli. Clear increases in [HbT], [HbO2], and [HHb] follow both noxious and innocuous stimulation (right).
- Figure 9.
Hemodynamic and EEG responses to innocuous control and to noxious heel lance are related. Scatterplots show a strong positive correlation between hemodynamic and EEG responses for the lance (left, n = 9) and control (right, n = 7) trials that were classified in the same way by the two cortical measures.
Tables
Demographic information No. infants 36 Age at birth (weeks) 39.0 (36.3–42.0) Age at study (weeks) 39.2 (36.6–43.3) Postnatal age at study (d) 2 (0–16) Female infants 15/36 Infants receiving right heel stimulation 20/36 Weight at birth (g) 3257 (1920–4750) Cesarean deliveries 18/36 Data are shown as the median (range) or as n/N and refer to number of infants, unless otherwise indicated.
Lance Control Touch Total sample included 17 20 16 (145) NIRS accepted 15 18 16 (131) EEG accepted 16 16 11 (106) Data refer to the number of infants; parentheses indicate the number of touches across all infants.
- Table 3.
Peak amplitude and latency of the grand average hemodynamic response to lance, control, and touch
Early peak Undershoot/overshoot [HbT] [HbO2] [HHb] [HbT] [HbO2] [HHb] Lance Amplitude, µm 2.3 ± 2.9 2.0 ± 2.2 0.5 ± 1.5 −1.3 ± 1.9 −1.3 ± 1.5 0.7 ± 1.4 Latency, s 3.2 3.4 3.2 10 9 10.6 Control Amplitude, µm 0.6 ± 1.1 0.4 ± 0.6 NS −0.5 ± 0.8 −0.5 ± 0.6 NS Latency, s 2.8 2.2 NS 12.4 13.4 NS Touch Amplitude, µm 0.2 ± 0.3 0.3 ± 0.2 NS NS NS −0.1 ± 0.2 Latency, s 2.8 4.0 NS NS NS 9.8 Amplitude is shown as the mean ± SD. Early peak, initial response occurring between 1.0 and 6.5 s; undershoot/overshoot, next identifiable peak occurring after 6.5 s; NS, not significant.
Lance Control Touch N2 Amplitude, µV −5.0 ± 12.2 −5.1 ± 15.5 −9.1 ± 10.1 Latency, ms 139 93 147 P2 Amplitude, µV 8.7 ± 16.6 20.1 ± 20.1 9.5 ± 8.4 Latency, ms 202 189 248 N3 Amplitude, µV −12.8 ± 12.1 Latency, ms 385 P3 Amplitude, µV 12.7 ± 17.1 Latency, ms 554 Data are shown as the mean ± SD.
NIRS HbO2 Present Absent EEG Present 6 2 8 N3P3 Absent 3 3 6 9 5 14 Location Data structure Type of test Confidence interval a (Fig. 2C) HbO2 GOF values but not HbO2 peak values are normally distributed Spearman’s ρ −0.03 to 0.86 b (Fig. 2D) N3P3 PC weights but not N3P3 amplitudes are normally distributed Spearman’s ρ 0.39–0.98 c HbO2 GOF values and N3P3 PC weights are both normally distributed Pearson’s r 0.15–0.96 d HbO2 GOF values but not N2P2 PC weights are normally distributed Spearman’s ρ −0.22 to 0.89
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