Vera Nenadovic

Phase synchronization measurements using electroencephalographic recordings: what can we really say about neuronal synchrony?

Phase synchrony analysis is a relatively new concept that is being increasingly used on neurophysiological data obtained through different methodologies. It is currently believed that phase synchrony is an important signature of information binding between distant sites of the brain, especially during cognitive tasks. Electroencephalographic (EEG) recordings are the most widely used recording technique for recording brain signals and assessing phase synchrony patterns. In this study, we address the suitability of phase synchrony analysis in EEG recordings. Using geometrical arguments and numerical examples, employing EEG and magnetoencephalographic data, we show that the presence of a common reference signal in the case of EEG recordings results in a distortion of the synchrony values observed, in that the amplitudes of the signals influence the synchrony measured, and in general destroys the intended physical interpretation of phase synchrony.

Decreased brain coordinated activity in autism spectrum disorders during executive tasks: Reduced long-range synchronization in the fronto-parietal networks

Current theories of brain function propose that the coordinated integration of transient activity patterns in distinct brain regions is the essence of brain information processing. The behavioural manifestations of individuals with autism spectrum disorders (ASD) suggest that their brains have a different style of information processing. Specifically, a current trend is to invoke functional disconnection in the brains of individuals with ASD as a possible explanation for some atypicalities in the behaviour of these individuals. Our observations indicate that the coordinated activity in brains of children with autism is lower than that found in control participants. Disruption of long-range phase synchronization among frontal, parietal and occipital areas was found, derived from magnetoencephalographic (MEG) recordings, in high-functioning children with ASD during the performance of executive function tasks and was associated with impaired execution, while enhanced long-range brain synchronization was observed in control children. Specifically, a more significant prefrontal synchronization was found in control participants during task performance. In addition, a robust enhancement in synchrony was observed in the parietal cortex of children with ASD relative to controls, which may be related to parietal lobe abnormalities detected in these individuals. These results, using synchronization analysis of brain electrical signals, provide support for the contention that brains of individuals with autism may not be as functionally connected as that of the controls, and may suggest some therapeutic interventions to improve information processing in specific brain areas, particularly prefrontal cortices.

Fluctuations in Cortical Synchronization in Pediatric Traumatic Brain Injury

Traumatic brain injury (TBI) is the leading cause of death and acquired disability in the pediatric population worldwide. We hypothesized that electroencephalography (EEG) synchrony and its temporal variability, analyzed during the acute phase following TBI, would be altered from that of normal children and as such would offer insights into TBI pathophysiology. Seventeen pediatric patients with mild to severe head injury admitted to a pediatric critical care unit were recruited along with 10 age- and gender-matched controls. Patients had two electroencephalographs performed 3 days apart. Outcome was measured at 1 year post-TBI utilizing the Pediatric Cerebral Performance Category score (PCPC). Maximal synchrony between EEG channels correlated to areas of primary injury as seen on computed tomography (CT) scan. The temporal variability of phase synchronization among EEG electrodes increased as patients recovered and emerged from coma (p < 0.001). This temporal variability correlated with outcome (Pearson coefficient of 0.74) better than the worst Glasgow Coma Scale score, length of coma, or extent of injury on CT scan. This represents a novel approach in the evaluation of TBI in children.

Experimental observation of increased fluctuations in an order parameter before epochs of extended brain synchronization

The identification of epileptic seizure precursors has potential clinical relevance. It is conjectured that seizures may be represented by dynamical bifurcations and that an adequate order parameter to characterize brain dynamics is the phase difference in the oscillatory activity of neural systems. In this study, the critical point hypothesis that seizures, or more generally periods of widespread high synchronization, represent bifurcations is empirically tested by monitoring the growth of fluctuations in the putative order parameter of phase differences between magnetoencephalographic and electroencephalographic signals in nearby brain regions in patients with epilepsy and normal subjects during hyperventilation. Implications of the results with regard to epileptic phenomena are discussed.

Phase synchronization in electroencephalographic recordings prognosticates outcome in paediatric coma.

Brain injury from trauma, cardiac arrest or stroke is the most important cause of death and acquired disability in the paediatric population. Due to the lifetime impact of brain injury, there is a need for methods to stratify patient risk and ultimately predict outcome. Early prognosis is fundamental to the implementation of interventions to improve recovery, but no clinical model as yet exists. Healthy physiology is associated with a relative high variability of physiologic signals in organ systems. This was first evaluated in heart rate variability research. Brain variability can be quantified through electroencephalographic (EEG) phase synchrony. We hypothesised that variability in brain signals from EEG recordings would correlate with patient outcome after brain injury. Lower variability in EEG phase synchronization, would be associated with poor patient prognosis. A retrospective study, spanning 10 years (2000–2010) analysed the scalp EEGs of children aged 1 month to 17 years in coma (Glasgow Coma Scale, GCS, <8) admitted to the paediatric critical care unit (PCCU) following brain injury from TBI, cardiac arrest or stroke. Phase synchrony of the EEGs was evaluated using the Hilbert transform and the variability of the phase synchrony calculated. Outcome was evaluated using the 6 point Paediatric Performance Category Score (PCPC) based on chart review at the time of hospital discharge. Outcome was dichotomized to good outcome (PCPC score 1 to 3) and poor outcome (PCPC score 4 to 6). Children who had a poor outcome following brain injury secondary to cardiac arrest, TBI or stroke, had a higher magnitude of synchrony (R index), a lower spatial complexity of the synchrony patterns and a lower temporal variability of the synchrony index values at 15 Hz when compared to those patients with a good outcome.

Synchronous fluctuation in broad-band processes and application to the electroencephalographic brain data

We propose phase-like characteristics in the broad-band process and introduce a novel wavelet-based method to analyze fluctuation in synchrony (FIS) in a wide frequency range. We demonstrate FIS between multifractal processes and a modeled dynamical system in phase transition. We then apply the idea to analyze surface scalp electroencephalographic data from normal subjects and traumatic brain-injured (TBI) patients. Our results show that FIS in normal subjects is more pronounced and exhibits more dynamic spatiotemporal patterns. Moreover, we find an intrinsic synchrony-variability relationship underlying these FIS characteristics.

Bedside functional brain imaging in critically-ill children using high-density EEG source modeling and multi-modal sensory stimulation

Acute brain injury is a common cause of death and critical illness in children and young adults. Fundamental management focuses on early characterization of the extent of injury and optimizing recovery by preventing secondary damage during the days following the primary injury. Currently, bedside technology for measuring neurological function is mainly limited to using electroencephalography (EEG) for detection of seizures and encephalopathic features, and evoked potentials. We present a proof of concept study in patients with acute brain injury in the intensive care setting, featuring a bedside functional imaging set-up designed to map cortical brain activation patterns by combining high density EEG recordings, multi-modal sensory stimulation (auditory, visual, and somatosensory), and EEG source modeling. Use of source-modeling allows for examination of spatiotemporal activation patterns at the cortical region level as opposed to the traditional scalp potential maps. The application of this system in both healthy and brain-injured participants is demonstrated with modality-specific source-reconstructed cortical activation patterns. By combining stimulation obtained with different modalities, most of the cortical surface can be monitored for changes in functional activation without having to physically transport the subject to an imaging suite. The results in patients in an intensive care setting with anatomically well-defined brain lesions suggest a topographic association between their injuries and activation patterns. Moreover, we report the reproducible application of a protocol examining a higher-level cortical processing with an auditory oddball paradigm involving presentation of the patients own name. This study reports the first successful application of a bedside functional brain mapping tool in the intensive care setting. This application has the potential to provide clinicians with an additional dimension of information to manage critically-ill children and adults, and potentially patients not suited for magnetic resonance imaging technologies.

Hypsarrhythmia in epileptic spasms: Synchrony in chaos

PURPOSE Hypsarrhythmia is an electroencephalographic pattern associated with epileptic spasms and West syndrome. West syndrome is a devastating epileptic encephalopathy, originating in infancy. Hypsarrhythmia has been deemed to be the interictal brain activity, while the electrodecremental event associated with the spasms is denoted as the ictal event. Though characterized as chaotic, asynchronous and disorganized based on visual inspection of the EEG, little is known of the dynamics of hypsarrhythmia and how it impacts the developmental arrest of these infants. METHODS As an exploratory and feasibility study, we explored the dynamics of both hypsarrhythmia and electrodecremental events with EEG phase synchronization methods, and in a convenience sample of three outpatients with epileptic spasms. As ictal events are associated with prolonged phase synchronization, we hypothesized that if hypsarrhythmia was indeed the interictal brain activity that it would have lower phase synchronization than the electrodecremental event (ictal phase). RESULTS We calculated both the phase synchronization index and the temporal variability of the index in three patients with infantile spasms. Two patients had hypsarrhythmia and electrodecremental events and one had hemi-hypsarrhythmia. We found that the hypsarrhythmia pattern was a more synchronized state than the electrodecremental event. CONCLUSIONS We have observed that the hypsarrhythmia pattern may represent a more synchronized state than the electrodecremental event in infants with epileptic spasms. However, larger studies are needed to replicate and validate these findings. Additionally, further inquiry is required to determine the impact that increased synchronization may have on developmental outcomes in infants with epileptic spasms.

5. Prospective pre-emptive EEG study prior to west syndrome

Since the original description of hypsarrhythmia by visual inspection as a “chaotic” and disorganized pattern in 1954, we have continued this clinical practice of EEG interpretation with solely visual inspection until the present day. The description of hypsarrhythmia as “chaotic” [Gibbs EL, Fleming MM, Gibbs FA. Pediatrics 1954;13(1):66–73], was challenged by van Putten and Stam 17 years ago [IEEE Eng Med Biol Mag. 2001;20(5):72–9]. We are now conducting the first prospective study in newborn babies with risk factors for infantile spasms. Our rational is that 40 out of the 200 known risk factors can be detected during the neonatal period. After consent, we conduct the longitudinal EEG protocol every 2 months until 1 year of age. Phase synchrony and variability analyses are performed to detect the earliest EEG changes before hypsarrhythmia onset. The EEG analyses from the dynamics perspective opens a new examination of hypsarrhythmia and electrodecremental events (EDEs) in infantile spasms, beyond the sole visual inspection of the EEG. We will present cases to illustrate the value of the phase synchronization index and the temporal variability of the index. Preliminary data suggest that both abnormal EEG patterns, hypsarrhythmia and EDEs are associated with high phase synchronization. These preliminary findings question the prevailing notion that hysparrhythmia is a disorganized pattern and may account for the observed developmental stagnation in these children. The visual inspection of hypsarrhythmia does not appear sufficient to appreciate the highly synchronized EEG pattern in patients with infantile spasms.