Comparison of the DFA and Whittle exponents with the shuffled data.

<p>The DFA (<b>A</b>) and Whittle (<b>B</b>) exponents for each subject (vertical lines, averaged across channels) are clearly distinct from the pooled probability distributions of exponents formed from 5000 shuffled sequences. The exponents from the IEI sequences were found to be significantly different from the shuffled distributions (P<0.001) using the one sample Wilcoxon signed rank test, indicating LRTCs in the IEI sequences of all subjects studied. The data is plotted here using the same format as <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031543#pone-0031543-g004" target="_blank">Figure 4 </a><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031543#pone.0031543-LinkenkaerHansen4" target="_blank">[10]</a>.</p

Hurst exponent estimates in relation to subject age.

<p>Whittle (stars) and DFA exponents (circles) were calculated for each subject for the whole IEI sequence (<b>A</b>) and fixed length sequences of the first 1000 IEIs (<b>B</b>). Each point is the exponent calculated for a single IEI sequence from a single channel. These are plotted against the corrected age (gestational plus time since birth). Arrows indicate subjects with intracranial haemorrhages (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031543#pone-0031543-t001" target="_blank">Table 1</a>). DFA exponents are calculated using a maximum window size of 1/4.</p

Averaged DFA plots and comparison with shuffled distributions for fixed length IEI sequences.

<p>(<b>A</b>) Average (across channels) DFA plots of window size, n, against root mean square fluctuation, F(n), for each subject for the first 1000 IEIs. DFA is calculated up to a maximum box size of 1/4 of the length of the signal i.e. 250. Exponents are as indicated. (<b>B,C</b>) Averaged DFA (<b>B</b>) and Whittle (<b>C</b>) exponents (vertical lines) for each subject from sequences of the first 1000 IEIs, along with the probability distributions of the shuffled data.</p

Subject Information.

<p><b>1</b> Subject information. Ages are given as weeks+days. Two different bipolar montages were used. 1 = F4-C4, C4-O2, F3-C3, C3-O1, T4-C4, C4-Cz, Cz-C3, C3-T3, 2 = F4-C4, C4-P4, P4-O2, F3-C3, C3-P3, P3-O1, T4-C4, C4-Cz, Cz-C3, C3-T3. Remaining electrodes indicates those electrodes used for analysis after artefact rejection and removal of short (<1000) IEI sequences – see methods. Electrodes are numerically indexed corresponding to the list here. Number of events per hour is averaged across all (remaining) electrodes. Subjects with haemorrhages (*) had significantly lower number of events per hour – two sample t-test, P = 1.4×10⁻¹⁴. Ultrasound details are indicated by N = normal, A = intraventricular/parenchymal haemorrhage (grade 4) left hemisphere, intraventricular haemorrhage (grade 3) right hemisphere, B = left germinal matrix haemorrhage, grade 4, C = bilateral germinal matrix haemorrhage grade 1 and cystic changes in post ventricular white matter and D = bilateral intraventricular haemorrhage involving parenchyma on right, grade 3 left, grade 4 right. Further details provide known follow up details for each subject. One child (subject 7) died of non-neurological complications of prematurity.</p

Inter-event interval (IEI) sequence and detrended fluctuation analysis (DFA) estimates.

<p>(<b>A</b>) An example of an IEI sequence – produced from the sequential ordering of IEI. This sequence is from the C3-O1 bipolar recording of subject 5. Index indicates the sequential order of the IEI. (<b>B</b>) An example of a randomly shuffled sequence for the data set shown in (<b>A</b>). (<b>C</b>) DFA plot for both sequences with window size, n, against root mean square fluctuation, F(n), open circles - DFA of the actual IEI sequence, filled circles - DFA of the shuffled sequence shown in (<b>B</b>). DFA was calculated with a maximum window size of 1/10 of the length of the sequence. For each the line of best fit is shown (green for the actual IEI sequence, red for the shuffled sequence). The Hurst exponent is estimated by the slope of the line of best fit which in these cases were H = 0.66 and H = 0.49 for the IEI and shuffled sequences respectively.</p

Characteristics of seizures and anticonvulsant administration in each neonate.

<p>Vertical red lines denote the presence of electrographic-only seizures, vertical blue lines denote electroclinical seizures and vertical green lines denote obscured seizures. Horizontal black line denotes the period of EEG monitoring. Black crosses denote missing data. Timepoints bounded by black arrows denote the first-line anticonvulsant administration while the magenta arrows denote the second-line anticonvulsant administration.</p

Demographics and neuroimaging features of neonates in the order of increasing seizure burden.

<p>EMCS, emergency Caesarean section; FTP, failure to progress; LLL, left lower limb clonic; LMCA, left middle cerebral artery; LPCA, left posterior cerebral artery; LS, left-sided clonic; LUL, left upper limb clonic movements; NRCTG, non-reassuring cardiotocogram; PROM, premature rupture of membranes; RMCA, right middle cerebral artery; RS, right-sided clonic; RUL, right upper limb clonic; VV, vertex vaginal.</p

Characteristics of EEG and seizures.

<p>Subtle seizures: C, cycling movements of the limbs; D, desaturations; M, mouthing and smacking; S, sucking; Y, yawning.</p

A. EEG in a neonate (case 6).

<p>Seizures arising from the left hemisphere corresponding with a left middle cerebral artery infarction on cranial MRI. <b>B. Cranial MRI in a neonate (case 6).</b> The sequence is an axial T2 turbo spin echo performed on day 7 of life. Note the characteristic focal spike and wave discharges over the left hemisphere with phase reversal over the left central region.</p