Figure 2.
Electrical Analysis of Neuronal Lines, Minimum Embedding Dimension, and Clinical Correlations
(A) Raw MEA data. Raw electrode waveforms (top) are used for spike detection (bottom) and downstream analyses.
(B) Spike interval and bursting variables highlight electrophysiological differences. Group average values with 95% confidence intervals are given for several time points of two variables. Variation in the interspike interval and number of bursting electrodes does show significant group-based differences for day 15 and 17 between control (blue) and ASD (red). For each relevant panel, significance was as tested with Welch's two-sided t test and indicated by asterisks. ⁎p ≤ 5 × 10−2, ⁎⁎p ≤ 5 × 10−3, ⁎⁎⁎p ≤ 5 × 10−5, and ⁎⁎⁎⁎p ≤ 5 × 10−7.
(C) Overview of group-wise differences across spiking measures and MED. This binary matrix indicates at which time points a measure was able to detect a significant difference between cases and controls (black squares). The MED outperforms all measures in distinguishing groups, but it does overlap with some bursting and spike interval variables, as shown in (B). Relatively common measures, such as the mean firing rate, fail to distinguish control and ASD activity over any day of the recording period.
(D) MED offers a sustained and statistically significant separation of groups. Average MED values and 95% confidence intervals for both groups are depicted for the first eight time points. The control subjects (blue) are associated with higher MED complexity score in comparison with the ASD subjects (red). The dotted rectangle indicates the values of the MED during day 15 of the MEA recordings, when RNA sequencing was performed.
(E) MED is correlated to clinical endpoints of interest. Low MED scores, which are associated with ASD diagnosis, are correlated to lower Vineland adaptive behavior score (left) and lower early nonverbal IQ (right). The gray shading represents a 95% confidence interval around the fitted curve, as estimated by a linear model.
See also Figure S2.