Marjo Metsäranta

Early Development of Spatial Patterns of Power-Law Frequency Scaling in fMRI Resting-State and EEG Data in the Newborn Brain

Recent studies have revealed spatial and functional relations in the temporal dynamics of resting-state functional magnetic resonance imaging (rs-fMRI) or electroencephalography (EEG) signals recorded in the adult brain. By modeling the frequency power spectrum of resting-state brain signals with a power-law function 0(f)α1/fα, the power-law exponent α has been shown to relate to the connectivity patterns of spontaneous brain activity that forms so-called rs-fMRI networks in the human adult brain. Here, we present an analysis of the dynamic properties of rs-fMRI and EEG signals acquired both in the newborn and adult brain, and we demonstrate frequency scaling of a power-law kind for orders of magnitude in the hemodynamic (0.01-0.15 Hz) and the electrical (0.2-30 Hz) domain. We show that the spatial segregation of resting-state dynamics of intrinsic fMRI signals in terms of the power-law exponent α is closely related to previously delineated resting-state neuronal architecture that encompasses primary sensory cortices and associate cortex in newborns. Moreover, the spatial profiles of differences in temporal dynamics for rs-fMRI signals could also be observed in EEG measurements in the newborn brain, albeit at a coarser spatial scale, with larger power-law exponents in occipital and parietal cortices compared with signals from the frontal brain.

Functional Bimodality in the Brain Networks of Preterm and Term Human Newborns

The spontaneous brain activity exhibits long-range spatial correlations detected using functional magnetic resonance imaging (fMRI) signals in newborns when (1) long neuronal pathways are still developing, and (2) the electrical brain activity consists of developmentally unique, intermittent events believed to guide activity-dependent brain wiring. We studied this spontaneous electrical brain activity using multichannel electroencephalography (EEG) of premature and fullterm babies during sleep to assess the development of spatial integration during last months of gestation. Correlations of frequency-specific amplitudes were found to follow a robust bimodality: During low amplitudes (low mode), brain activity exhibited very weak spatial correlations. In contrast, the developmentally essential high-amplitude events (high mode) showed strong spatial correlations. There were no clear spatial patterns in the early preterm, but clear frontal and parieto-occipital modules at term age. A significant fronto-occipital gradient was also seen in the development of the graph measure clustering coefficient. Strikingly, no bimodality was found in the fMRI recordings of the fullterm babies, suggesting that early EEG activity and fMRI signal reflect different mechanisms of spatial coordination. The results are compatible with the idea that early developing human brain exhibits intermittent long-range spatial connections that likely provide the endogenous guidance for early activity-dependent development of brain networks.

High-fidelity recording of brain activity in the extremely preterm babies: Feasibility study in the incubator

OBJECTIVE To develop an electrode cap with high number of electrodes for recording very small preterm babies, to assess the physiological stress imposed by the application of this cap on babies, and to estimate what added information could be potentially obtained with more electrodes in this age group. METHODS We recruited eleven extremely small preterm babies (conceptional age 25-29 weeks) to record their EEG with a custom-tailored high-density EEG cap (20 channels), coupled with a Full-band EEG amplifier. Physiological stress caused by the cap placement was assessed by recording heart rate and arterial oxygen saturation before and during EEG cap placement, as well as before and during a routine care procedure of the given baby. The quality of novel information obtained with this system was assessed by comparing the full signal to a set of EEG signals where we deliberately distorted and omitted major signal components to make it appear as in the conventional EEG systems. RESULTS The changes in heart rate or oxygen saturation caused by the cap placement are fully comparable to the changes seen after any normal care procedure in the same baby. Our recordings did also reveal that brain activity in the small premies is highly focal, and often confined to only one or two electrodes. Hence it cannot be pertinently localized with the currently used low number of recording electrodes. Moreover, recordings from babies with focal intracerebral hemorrhages showed that changes after vascular insults are clearly more prominent and hence easier to detect visually from multichannel recordings. CONCLUSIONS Recording of high-fidelity EEG (high-density caps and FbEEG system) is practical in the incubator environment, and the application of a proper EEG cap is not more stressful to the baby than a routine care procedure. Moreover, these achievable amendments in the recording system seem to disclose major physiological and pathological signal components in the as yet poorly explored patient group. SIGNIFICANCE Introduction of a technically feasible and physically gentle enough EEG recording system will enable further development of clinical neurophysiological understanding, as well as the design of pertinent brain monitors, which is urgently needed in these patients.

Phase synchrony in the early preterm EEG: development of methods for estimating synchrony in both oscillations and events.

Development of neuronal connections relies on proper neuronal activity, and it starts during the time when early preterm babies are treated in the neonatal intensive care units. While synchrony has been a key element in visual assessment of neonatal EEG signals, there has been no unambiguous definitions for synchrony, and no objective measures available for neonatal signals. Estimation of phase locking value (PLV) has been an established paradigm in adults, but many unique characteristics of the neonatal EEG have precluded its applicability in them. In the present paper, we developed the existing PLV-based methods further to be applicable for neonatal signals at two different temporal scales, oscillations and events, where the latter refers technically to quantitating phase synchrony (PS) between band-specific amplitude envelopes (bafPS). In addition, we present a measure for quantitation based on assessing cumulative proportion of time with statistically significant synchrony between the given signal pair. The paper uses real EEG examples and the prior neurobiological knowledge in the process of defining optimal parameters in each step of the procedure. Finally, we apply the method to a set of dense array EEG recordings from very early preterm babies, recorded at conceptional age of less than 30 weeks. By comparing PS and bafPS from babies without and with major cerebrovascular lesion, we show that the effects of brain lesions may be selective both in space and in frequency. These findings do by nature escape visual detection in the conventional EEG reading, however they have intriguing correlates in the current concept of how somatosensory networks are thought to develop and/or become disorganized in the early preterm babies.

Decreasing perinatal mortality in placental abruption.

Objective. To study perinatal mortality associated with placental abruption. Design. Retrospective population study using the Finnish Hospital Discharge Register and Medical Birth Register data. Setting. Finland, 1987–2005. Population. Pregnancies with placental abruption and all other births without placental abruption. Methods. The national Hospital Discharge Register and Medical Birth Register were used to identify all pregnancies with placental abruption. Demographic data and delivery outcomes were collected retrospectively. Perinatal mortality associated with placental abruption was compared with that in other births. Potential risk factors were analysed. Main outcome measures. Perinatal mortality in placental abruption. Results. The study consisted of 618 735 women with 1.14 million pregnancies, 4336 of whom had placental abruption. Overall perinatal mortality with abruption was 119 per 1000 births. Placental abruption explained 7% of all perinatal deaths. The mortality among singleton births (125 per 1000) was higher than among multiple births (40 per 1000). The majority of deaths (77%) occurred in utero. Singleton perinatal mortality with abruption decreased from 173 per 1000 in 1987–1990 to 98 per 1000 in 2000–2005 (p < 0.001). In singleton births at <32 gestational weeks, overall perinatal mortality was high (345 per 1000) and was not increased by placental abruption. Prematurity, low birthweight, male fetal sex and maternal smoking were independent risk factors for placental abruption‐related perinatal mortality. Conclusions. Although mortality associated with placental abruption decreased during the study period, placental abruption still remains an important cause of perinatal mortality.

Maternal deaths in Finland: Focus on placental abruption

Objective. To study placental abruption‐associated maternal deaths out of all maternal deaths in Finland. Design. Register‐based study. Setting. The Finnish Medical Birth Register (MBR), the Hospital Discharge Register (HDR), and the Cause‐of‐Death Register data during 1972–2005. Methods. The maternal deaths were identified by linking data from the MBR, the HDR, and the Cause‐of‐Death Register. The clinical data were collected from the case records and death certificates. Main outcome measures. Cause‐specific maternal death with special reference to placental abruption. Results. During the study period, a total of 2,104,436 live births and 117 direct maternal deaths (caused by a disease or its management unique to the pregnancy) occurred in Finland. The direct maternal mortality ratio (MMR) was 5.6 per 100,000 live births. The two leading causes were thromboembolism (24.0%) and hemorrhage (22.3%) representing almost half of all maternal deaths. Altogether 7,735 placental abruptions were identified with three maternal deaths giving a case fatality rate of 0.4 per 1,000 cases. The MMR (38.8 per 100,000) was nearly seven times higher than the overall MMR (5.7 per 100,000) (p = 0.010). Conclusion. The direct MMR in Finland is at the level generally seen in Western Europe. The main causes to maternal death are thromboembolism and obstetric hemorrhage. Deaths to placental abruption are rare, but still seven times higher than the overall MMR.

Does very premature birth affect the functioning of the somatosensory cortex? — A magnetoencephalography study

Increased survival of extremely low birth weight infants has led to a need for new prognostic methods to predict possible future neurological impairment. We investigated the early development of the somatosensory system by recording the somatosensory evoked magnetic fields (SEFs) during natural sleep at fullterm age in 16 very prematurely born infants and 16 healthy newborns born at term. The purpose was to determine possible changes in the function of the somatosensory cortex in the prematurely born infants by comparing the latency, strength, location and morphology of the SEFs with those of healthy fullterm newborns. We recorded reliable SEFs in all patients and controls. The equivalent current dipole (ECD) strength of the first cortical response, M60, was significantly lower in the patients. Otherwise, the general morphology and latency of the SEFs were similar in the two groups of babies. The similar response latencies in the two groups indicate normally developed conduction in the somatosensory system of the prematurely born infants. The attenuated ECD strength may reflect weaker synchrony in firing or a smaller number of the cortical neurons activated by the somatosensory stimulation. At the individual level, in four of the preterm infants, a later M200 response was not present or could not be modeled: all of them had lesions of the underlying hemisphere depicted by ultrasound and magnetic resonance imaging.

Preterm EEG: a multimodal neurophysiological protocol.

Since its introduction in early 1950s, electroencephalography (EEG) has been widely used in the neonatal intensive care units (NICU) for assessment and monitoring of brain function in preterm and term babies. Most common indications are the diagnosis of epileptic seizures, assessment of brain maturity, and recovery from hypoxic-ischemic events. EEG recording techniques and the understanding of neonatal EEG signals have dramatically improved, but these advances have been slow to penetrate through the clinical traditions. The aim of this presentation is to bring theory and practice of advanced EEG recording available for neonatal units. In the theoretical part, we will present animations to illustrate how a preterm brain gives rise to spontaneous and evoked EEG activities, both of which are unique to this developmental phase, as well as crucial for a proper brain maturation. Recent animal work has shown that the structural brain development is clearly reflected in early EEG activity. Most important structures in this regard are the growing long range connections and the transient cortical structure, subplate. Sensory stimuli in a preterm baby will generate responses that are seen at a single trial level, and they have underpinnings in the subplate-cortex interaction. This brings neonatal EEG readily into a multimodal study, where EEG is not only recording cortical function, but it also tests subplate function via different sensory modalities. Finally, introduction of clinically suitable dense array EEG caps, as well as amplifiers capable of recording low frequencies, have disclosed multitude of brain activities that have as yet been overlooked. In the practical part of this video, we show how a multimodal, dense array EEG study is performed in neonatal intensive care unit from a preterm baby in the incubator. The video demonstrates preparation of the baby and incubator, application of the EEG cap, and performance of the sensory stimulations.

An Easy and Practical Method for Routine, Bedside Testing of Somatosensory Systems in Extremely Low Birth Weight Infants

This study was set out to develop and describe a novel, simple, and safe method for routine bedside testing of somatosensory system in very early preterm infants. We recorded electroencephalogram (EEG) activity after tactile stimulation of hand (palm) and foot (sole) by a soft hairbrush stimulator in extremely low birth weight infants (n = 10; GA, 24–28, recording at conceptional age 30–32 wk) and compared with the raw EEG responses to those seen by one- or two-channel brain monitors. In every subject, single tactile stimuli produced prominent (100–350 μV) somatosensory evoked responses (SERs) that were readily identified in the ongoing EEG signal. The maximal SER was in the contralateral hemisphere at around the corresponding somatosensory representation areas. Conventional EEG filtering did significantly reduce the SERs, but they could still be identified in the routine brain monitor setting widely available in NICUs. The method described here is directly applicable to assessment of integrity of somatosensory system in the early preterm period. It needs minimal training and requires an EEG system or a brain monitor device that is available in most units. Thus, the technique is likely to open a novel window to neurologic assessment of these babies.

Probabilistic atlas can improve reconstruction from optical imaging of the neonatal brain

Diffuse optical imaging is an emerging medical imaging modality based on near-infrared and visible red light. The method can be used for imaging activations in the human brain. In this study, a deformable probabilistic atlas of the distribution of tissue types within the term neonatal head was created based on MR images. The use of anatomical prior information provided by such atlas in reconstructing brain activations from optical imaging measurements was studied using Monte Carlo simulations. The results suggest that use of generic anatomical information can greatly improve the spatial accuracy and robustness of the reconstruction when noise is present in the data.