Increase in active electrode firing fraction and spatial coherence of electrical activity after drug addition.

<p><b>a:</b> Area under the curve (AUC), a numerical integration, of the total firing fraction between baseline and post-drug periods shows significant increase (** p < 0.01, *** p < 0.001) after KCl (p = 0.0009) and PTZ (p = 0.002) addition relative to baseline. Note the similarity in the firing fraction across time when no drug (sham) was added to the bath (p = 0.86). <b>b:</b> Area under the curve of spatial coherence, a measure derived by comparing the correlation of coefficient of a central pixel with respect to its nearest-matching neighbor along time, also did not differ between baseline and follow-up in the sham condition (p = 0.19). Notably, more channels fired simultaneously indicating a significant increase (* p < 0.05, ** p < 0.01) in spatial coherence after KCl (p = 0.002) and PTZ (p = 0.02) administration.</p

Tools and steps for larva-mounting and timeline of recording.

<p><b>a:</b> Electrode chamber used for recordings (scale: 10 mm). <b>b:</b> Nylon mesh and slice anchor used to hold larva in place (scale: 5 mm). <b>c:</b> Placement of larva onto its dorsal side into the chamber with a drop of water (scale: 300 μm). <b>d:</b> Securing larva with nylon mesh (scale: 300 μm); microelectrode array is highlighted with red dots for enhanced visibility in this photo and the next. <b>e:</b> Larva positioned with head onto the microelectrode array (scale 300 μm). <b>f:</b> Timeline for experiments—each starting with a 15 min acclimation period, a 30 min control recording, and a 30 min recording time after drug application.</p

Confirmation of cell stability.

<p>Top panels in (<b>a)</b> show representative single cell recordings before and after KCl addition, top panels in (<b>b</b>) before and after PTZ addition. Bottom panels show averages of baseline and KCl recordings (<b>a</b>) and of baseline and PTZ recordings (<b>b</b>). Dashed lines indicate the width of the averaged action potential at half maximum of the amplitude and they approximate 1.3 ms in both recordings. Action potentials are stable over time as indicated by the unchanged shape of the traces.</p

Provoked seizures in 5-second raw data traces of action potentials.

<p><b>a:</b> Baseline activity before PTZ addition. <b>b:</b> A typical seizure starting with a prolonged action potential burst 1–2 minutes after PTZ application. <b>c:</b> Seizures continue as short paroxysmal action potential bursts. PTZ addition leads to a seizure firing pattern. Markings denote sustained (> 2 sec; b) versus short (< 500 ms; c) bursting.</p

Spike rate as a function of time.

<p>Spike rate is plotted as a function of time (bin size: 1s)–one channel per condition is shown. No significant change in burst or firing rate follows a sham convulsant application (<b>a</b>). Epileptic activity is detected as increased action potential firing rate and bursting after the addition of 15 mM KCl (<b>b</b>) or 15 mM PTZ (<b>c</b>). Spike rate increases with drug addition.</p

Spike rate and burst rate increase after drug-addition.

<p><b>a:</b> Summary statistics of recordings from all active channels show a significant increase (** p < 0.01) in spike rate across all experiments following KCl (p = 0.001) or PTZ addition (p = 0.001) to the bath in contrast to the sham condition (p = 0.87). <b>b:</b> Summary statistics of recordings from all active channels show a significant increase (* p < 0.05, *** p < 0.001) of bursting across all experiments following KCl (p = 0.0006) and PTZ addition (p = 0.02) to the bath in contrast to the sham-condition (p = 0.53). The addition of the chemical convulsants KCl and PTZ leads to an increase in firing and bursting of action potentials.</p

EEG and action potential recordings.

<p>Both EEG- and action potential recordings from zebrafish larvae can be obtained simultaneously and correlated with each other. These recordings are taken from one channel following PTZ- administration. <b>a:</b> Data are filtered to show an EEG (bandpass at 1 to 25 Hz). <b>b:</b> Corresponding multi-unit activity (high pass at 100 Hz).</p

Addition of TTX to seizing larvae abolishes spiking.

<p>Spike rate plotted as a function of time (one channel shown). Recordings are made before and after PTZ addition. The addition of 0.4 mM TTX at 3900 s abolished firing. These experiments demonstrate a high likelihood that recorded signals arise from neurons firing action potentials (in contrast to myogenic potentials arising from tail-movements).</p

Inpatient resource utilization attributable to children with neurological impairment, Kids' Inpatient Database 1997, 2000, 2003, and 2006, by hospital type.

<p>These graphs describe the proportion of all pediatric inpatient health resources attributable to NI from each year. Proportion (with 95% confidence interval) of total number of hospitalizations, hospital bed days, and total aggregate charges are shown for all hospitals, non-children's hospitals, and children's hospitals. Each bar represents 1 y of data. The four bars in each group represent data from 1997, 2000, 2003, and 2006.</p

Neurological impairment diagnoses of hospitalized children, Kids' Inpatient Database 1997, 2000, 2003, and 2006.

<p>This graph describes the proportion of total NI hospitalizations attributable to each of the NI diagnosis categories.</p