Evaluating the Modulation of the Acoustic Startle Reflex in Children and Adolescents via Vertical EOG and EEG: Sex, Age, and Behavioral Effects

Abstract

Acoustic startle reflex (ASR) constitutes a reliable, cross-species indicator of sensorimotor and inhibitory mechanisms, showing distinct signature in cognitive aging, sex, and psychopathological characterization. ASR can be modulated by the prepulse inhibition (PPI) paradigm, which comprises the suppression of reactivity to a startling stimulus (pulse) following a weak prepulse (30- to 500-ms time difference), being widely linked to inhibitory capabilities of the sensorimotor system. If the prepulse-pulse tones are more clearly separated (500-2,000 ms), ASR amplitude is enhanced, termed as prepulse facilitation (PPF), reflecting sustained or selective attention. Our study aimed to investigate early-life sensorimotor sex/age differences using Electroencephalographic recordings to measure muscular and neural ASR in a healthy young population. Sixty-three children and adolescents aged 6.2-16.7 years (31 females) took part in the experiment. Neural ASR was assessed by two different analyses, namely, event-related potentials (ERPs) and first-derivative potentials (FDPs). As expected, PPF showed enhanced responses compared with PPI, as indicated by eyeblink, ERP and FDP measures, confirming the gating effect hypothesis. Sex-related differences were reflected in FDPs, with females showing higher ASR than males, suggesting increased levels of poststartle excitability. Intragroup age effects were evaluated via multipredictor regression models, noticing positive correlation between age versus eyeblink and ERP responses. Attention-related ERPs (N100 and P200) showed distinct patterns in PPI versus PPF, potentially indicative for alternative attentional allocation and block-out of sensory overload. Screening measures of participants' neurodevelopmental (assessed by Wechsler Intelligence Scale for Children) and behavioral (assessed by Child Behavior Checklist) markers were also associated with increased N100/P200 responses, presumably indexing synergy between perceptual consistency, personality profiling, and inhibitory performance. Conclusively, modulation of ASR by PPI and PPF is associated with biological sex and internal/external personality traits in childhood and adolescence, potentially useful to guide symptomatology and prevention of psychopathology.

Keywords: EEG; acoustic startle reflex; first-derivative potential; prepulse facilitation; prepulse inhibition; sensorimotor gating.

FIGURE 1

Trial structure of (A) prepulse inhibition (PPI) and (B) prepulse facilitation (PPF) conditions.

FIGURE 2

Processing steps for the classification between reflexive and nonreflexive trials based on the vertical electro-oculogram (VEOG) signal. (A) An example of a reflexive trial showing a strong blink immediately after startle onset. In step 4, it is shown that the poststartle Z score (within 20–150 ms) exceeds the threshold of 1 (dashed line), meaning that the blink is at least 1 SD above the prestartle –30- to 0-ms period. (B) An example of a nonreflexive trial showing the presence of a strong blink immediately before startle onset and a non–startle-related blink approximately 600 ms. In step 4, negative values of the poststartle Z scores (within 20–150 ms) indicate that the prestartle blink was dominant. Color-shaded areas highlight the prestartle (blue) and poststartle (green) windows of interest, as indicated by the legend at the bottom.

FIGURE 3

Collapsed ERP waveforms in three ROIs during –30 to 600 ms. (A) ERP wave for the P50 ROI and the P50 topographical distribution averaged across 20–60 ms poststartle. (B) ERP wave for the N100 ROI and the N100 topographical distribution averaged across 61–110 ms poststartle. (C) ERP wave for the P200 ROI and the P200 topographical distribution averaged across 111–230 ms poststartle. Color-shaded areas indicated the window elicitation of the aforementioned ERP components. Time 0 corresponds to the startle onset.

FIGURE 4

Characteristics of first-derivative potentials (FDPs). (A) A typical ERP wave with two dominant early peaks. (B) The respective FDP curve of ERP, indicating the peaks (zero values), positive-going (blue segments), and negative-going (red segments) of ERP. The temporal differentiation has been derived with Δt = 4 ms. (C) The absolute FDP curve, highlighting the segments of rapid (early gray-shaded area) and slow (late gray-shaded area) in ERP waveform. (D) The whole-scalp FDP averaged across subjects and conditions. The window of FDP burst (20–230 ms) is also gray-shaded. (E) The topographical map of the grand-average FDP within the window of 20–230 ms.

FIGURE 5

Grand-averaged VEOG responses for each group (males vs. females) and condition (prepulse inhibition, PPI, vs. prepulse facilitation, PPF). In panels (A,B), the time course of the VEOG responses is illustrated for males (PPI: blue, PPF: green) and females (PPI: red, PPF: orange), respectively, from –30 to 500 ms (time 0 is the startle onset). Color-shaded areas correspond to the time course of the standard error (± 1 SE) of the mean. In panels (C,D), the individual samples and descriptive statistics (mean and median) are depicted in scatter boxplots, separately for amplitudes and latencies, respectively. *Significance at p < 0.05.

FIGURE 6

Grand-averaged ERP responses for each group (males vs. females) and condition (PPI vs. PPF). (A–F) The time course of the component- and ROI-specific ERP responses are illustrated for males (PPI: blue, PPF: green) and females (PPI: red, PPF: orange), respectively, from –30 to 500 ms (time 0 is the startle onset). Color-shaded areas correspond to the time course of the standard error (± 1 SE) of the mean. ERP component topographies are shown on the right of each plot. (G–I) The descriptive statistics (mean and median) of condition main effects are depicted as scatter boxplots for each ERP component. *Significant differences between PPF and PPI.

FIGURE 7

Grand-averaged FDP responses for both groups and conditions. (A) The time course of the WS-FDP responses is illustrated for males (PPI: blue, PPF: green) and females (PPI: red, PPF: orange), respectively, from –30 to 500 ms (time 0 is the startle onset). Color-shaded areas correspond to the time course of the standard error (± 1 SE) of the mean. (B) The descriptive statistics (mean and median) of groups/conditions are depicted as scatter boxplots. (C) Topographical maps for averaged FDP during 20–230 ms poststartle.

FIGURE 8

Linear term of VEOG amplitudes in PPI correlating with age as scatterplots. (A) Age versus VEOG amplitudes in PPI in the whole population. (B) Age versus VEOG amplitudes in PPI in Males only. (C) Age versus VEOG amplitudes in PPI in females only. Color-shaded areas indicate the 95% confidence interval of the best-fitting line.

FIGURE 9

Linear terms of ERP amplitudes in PPF correlating with age as scatterplots. (A) Age versus N100 in PPF (left) and age versus P200 in PPF (right) in the whole population. (B) Age versus N100 in PPF for males subgroup. (C) Age versus P200 in PPF for females subgroup. Color-shaded areas indicate the 95% confidence interval of the best-fitting line.