Laskennalliset muuttujat vastasyntyneen aivomonitoroinnin arvioinnissa

The aim of this thesis was to find out if computational electroencephalography (EEG) features can be used in the automated monitoring of newborns after asphyxia. EEG is already widely used in the neonatal intensive care units but there is a need for quantitative measures that can be obtained without the presence of a clinical expert. One of the biggest challenges in the treatment of newborns with asphyxia is also to correctly estimate the severity of the resulting neurological problems. Eight different feature classes were computed for 42 full-term babies from periods of quiet and active sleep. These feature classes measured correlations of amplitude and phase, interhemispheric synchrony, multifractality and spectral properties. We then studied the ability of these features to distinguish between different severity groups and also tested a classification algorithm to predict the outcome of the babies. Quiet sleep was noted to be more sensitive when separating groups with different grades of severity and most of the used feature classes showed significant results in statistical testing between the groups. The babies with the normal outcome were classified more accurately with the EEG based classification algorithm, than with only the clinical estimation.Työn tarkoituksena oli selvittää, onko aivosähkökäyrästä (EEG) laskettuja parametreja mahdollista käyttää happivajeesta kärsineiden vastasyntyneiden automaattisessa monitoroinnissa. EEG on jo nyt yleisesti käytössä vastasyntyneiden teho-osastoilla, mutta tarve kvantitatiivisille mittareille, joiden tulkintaan ei tarvita lääketieteen asiantuntijaa, on suuri. Lisäksi yksi suurimmista haasteista on pystyä arvioimaan tarkasti, kuinka vakaviin neurologisiin ongelmiin happivaje johtaa. Työssä laskettiin kahdeksan erilaista muuttujajoukkoa 42 täysiaikaiselle vauvalle sekä hiljaisen että aktiivisen unen aikana. Nämä muuttujat mittasivat amplitudin ja vaiheen korrelaatioita, aivopuoliskojen välistä synkroniaa, multifraktaalisuutta sekä taajuusjakaumaa. Tämän jälkeen tutkittiin muuttujien kykyä erotella eri vakavuusasteisia ryhmiä ja testattiin luokittelualgoritmia vauvojen tulevan terveydentilan ennustamiseen. Hiljaisen unen huomattiin olevan herkempi havaitsemaan eroja eri vakavuusasteisten ryhmien välillä ja tilastollisen testauksen perusteella suurin osa valituista muuttujajoukoista erotteli merkittävästi eri vakavuusryhmiä. Ne vauvat, jotka toipuivat hapenpuutteesta täysin, pystyttiin löytämään EEG-pohjaisella luokittimella tarkemmin kuin pelkän kliinisen arvion avulla

Identification of proprioceptive thalamocortical tracts in children : comparison of fMRI, MEG, and manual seeding of probabilistic tractography

Studying white matter connections with tractography is a promising approach to understand the development of different brain processes, such as proprioception. An emerging method is to use functional brain imaging to select the cortical seed points for tractography, which is considered to improve the functional relevance and validity of the studied connections. However, it is unknown whether different functional seeding methods affect the spatial and microstructural properties of the given white matter connection. Here, we compared functional magnetic resonance imaging, magnetoencephalography, and manual seeding of thalamocortical proprioceptive tracts for finger and ankle joints separately. We showed that all three seeding approaches resulted in robust thalamocortical tracts, even though there were significant differences in localization of the respective proprioceptive seed areas in the sensorimotor cortex, and in the microstructural properties of the obtained tracts. Our study shows that the selected functional or manual seeding approach might cause systematic biases to the studied thalamocortical tracts. This result may indicate that the obtained tracts represent different portions and features of the somatosensory system. Our findings highlight the challenges of studying proprioception in the developing brain and illustrate the need for using multimodal imaging to obtain a comprehensive view of the studied brain process.Peer reviewe

Variants in calcium voltage-gated channel subunit Alpha1 C-gene (CACNA1C) are associated with sleep latency in infants

Genetic variants in CACNA1C (calcium voltage-gated channel subunit alpha1 C) are associated with bipolar disorder and schizophrenia where sleep disturbances are common. In an experimental model, Cacna1c has been found to modulate the electrophysiological architecture of sleep. There are strong genetic influences for consolidation of sleep in infancy, but only a few studies have thus far researched the genetic factors underlying the process. We hypothesized that genetic variants in CACNA1C affect the regulation of sleep in early development. Seven variants that were earlier associated (genome-wide significantly) with psychiatric disorders at CACNA1C were selected for analyses. The study sample consists of 1086 infants (520 girls and 566 boys) from the Finnish CHILD-SLEEP birth cohort (geno-typed by Illumina Infinium PsychArray BeadChip). Sleep length, latency, and nightly awakenings were reported by the parents of the infants with a home-delivered questionnaire at 8 months of age. The genetic influence of CACNA1C variants on sleep in infants was examined by using PLINK software. Three of the examined CACNA1C variants, rs4765913, rs4765914, and rs2239063, were associated with sleep latency (permuted PPeer reviewe

Stronger proprioceptive BOLD-responses in the somatosensory cortices reflect worse sensorimotor function in adolescents with and without cerebral palsy

Cerebral palsy (CP) is a motor disorder where the motor defects are partly due to impaired proprioception. We studied cortical proprioceptive responses and sensorimotor performance in adolescents with CP and their typically-developed (TD) peers. Passive joint movements were used to stimulate proprioceptors during functional magnetic resonance imaging (fMRI) session to quantify the proprioceptive responses whose associations to behavioral sensorimotor performance were also examined. Twenty-three TD (15 females, age: mean +/- standard deviation 14.2 +/- 2.4 years) and 18 CP (12 females, age: mean +/- standard deviation, 13.8 +/- 2.3 years; 12 hemiplegic, 6 diplegic) participants were included in this study. Participants' index fingers and ankles were separately stimulated at 3 Hz and 1 Hz respectively with pneumatic movement actuators. Regions-of-interest were used to quantify BOLD-responses from the primary sensorimotor (SM1) and secondary (SII) somatosensory cortices and were compared across the groups. Associations between responses strengths and sensorimotor performance measures were also examined. Proprioceptive responses were stronger for the individuals with CP compared to their TD peers in SM1 (p < 0.001) and SII (p < 0.05) cortices contralateral to their more affected index finger. The ankle responses yielded no significant differences between the groups. The CP group had worse sensorimotor performance for hands and feet (p < 0.001). Stronger responses to finger stimulation in the dominant SM1 (p < 0.001) and both dominant and non-dominant SII (p < 0.01, p < 0.001) cortices were associated with the worse hand sensorimotor performance across all participants. Worse hand function was associated with stronger cortical activation to the proprioceptive stimulation. This association was evident both in adolescents with CP and their typically-developed controls, thus it likely reflects both clinical factors and normal variation in the sensorimotor function. The specific mechanisms need to be clarified in future studies.Peer reviewe

Gating Patterns to Proprioceptive Stimulation in Various Cortical Areas : An MEG Study in Children and Adults using Spatial ICA

Proprioceptive paired-stimulus paradigm was used for 30 children (10-17 years) and 21 adult (25-45 years) volunteers in magnetoencephalography (MEG). Their right index finger was moved twice with 500-ms interval every 4 ± 25 s (repeated 100 times) using a pneumatic-movement actuator. Spatial-independent component analysis (ICA) was applied to identify stimulus-related components from MEG cortical responses. Clustering was used to identify spatiotemporally consistent components across subjects. We found a consistent primary response in the primary somatosensory (SI) cortex with similar gating ratios of 0.72 and 0.69 for the children and adults, respectively. Secondary responses with similar transient gating behavior were centered bilaterally in proximity of the lateral sulcus. Delayed and prolonged responses with strong gating were found in the frontal and parietal cortices possibly corresponding to larger processing network of somatosensory afference. No significant correlation between age and gating ratio was found. We confirmed that cortical gating to proprioceptive stimuli is comparable to other somatosensory and auditory domains, and between children and adults. Gating occurred broadly beyond SI cortex. Spatial ICA revealed several consistent response patterns in various cortical regions which would have been challenging to detect with more commonly applied equivalent current dipole or distributed source estimates.peerReviewe

Cortical proprioceptive processing is altered in children with diplegic cerebral palsy

Children with cerebral palsy (CP) have various motor impairments, but less is known about the processing deficits of the somatosensory afference, especially in the proprioceptive domain. Proprioception (“the movement sense”) is behaviorally impaired primarily in the more affected hand of children with CP1,2 and bilaterally in the lower limbs2 . There are no prior studies quantifying the cortical proprioceptive processing in CP, but hand representation area is diminished to tactile stimuli in hemiplegic CP3 and the primary cortical response to tibial nerve stimulation is reduced in diplegic CP4.Peer reviewe

More comprehensive proprioceptive stimulation of the hand amplifies its cortical processing

Corticokinematic coherence (CKC) quantifies the phase coupling between limb kinematics and cortical neurophysiological signals reflecting proprioceptive feedback to the primary sensorimotor (SM1) cortex. We studied whether the CKC strength or cortical source location differs between proprioceptive stimulation (i.e., actuator-evoked movements) of right-hand digits (index, middle, ring and little). Twenty-one volunteers participated in magnetoencephalography measurements during which three conditions were tested: (1) simultaneous stimulation of all four fingers at the same frequency, (2) stimulation of each finger separately at the same frequency and (3) simultaneous stimulation of the fingers at finger-specific frequencies. CKC was computed between MEG responses and accelerations of the fingers recorded with three-axis accelerometers. CKC was stronger (p < 0.003) for the simultaneous (0.52 ± 0.02) than separate (0.45 ± 0.02) stimulation at the same frequency. Furthermore, CKC was weaker (p < 0.03) for the simultaneous stimulation at the finger-specific frequencies (0.38 ± 0.02) than for the separate stimulation. CKC source locations of the fingers were concentrated in the hand region of the SM1 cortex and did not follow consistent finger-specific somatotopic order. Our results indicate that that proprioceptive afference from the fingers is processed in partly overlapping cortical neuronal circuits, which was demonstrated by the modulation of the finger specific CKC strengths due to proprioceptive afference arising from simultaneous stimulation of the other fingers of the same hand as well as overlapping cortical source locations. Finally, comprehensive simultaneous proprioceptive stimulation of the hand would optimize functional cortical mapping to pinpoint the hand region, e.g., prior brain surgery.peerReviewe

Altered corpus callosum structure in adolescents with cerebral palsy : connection to gait and balance

Cerebral palsy (CP) is the most common motor disorder in childhood. Recent studies in children with CP have associated weakened sensorimotor performance with impairments in the major brain white-matter (WM) structure, corpus callosum (CC). However, the relationship between CC structure and lower extremity performance, specifcally gait and balance, remains unknown. This study investigated the transcallosal WM structure and lower limb motor stability performance in adolescents aged 10–18 years with spastic hemiplegic (n=18) or diplegic (n=13) CP and in their age-matched controls (n=34). The modern difusion-weighted MRI analysis included the difusivity properties of seven CC subparts and the transcallosal lower limb sensorimotor tract of the dominant hemisphere. Children with CP had comprehensive impairments in the cross-sectional area, fractional anisotropy, and mean difusivity of the CC and sensorimotor tract. Additionally, the extent of WM alterations varied between hemiplegic and diplegic subgroups, which was seen especially in the fractional anisotropy values along the sensorimotor tract. The difusion properties of transcallosal WM were further associated with static stability in all groups, and with dynamic stability in healthy controls. Our novel results clarify the mechanistic role of the corpus callosum in adolescents with and without CP ofering valuable insight into the complex interplay between the brain’s WM organization and motor performance. A better understanding of the brain basis of weakened stability performance could, in addition, improve the specifcity of clinical diagnosis and targeted rehabilitation in CP.peerReviewe

Cortical proprioceptive processing is altered in children with diplegic cerebral palsy

Children with cerebral palsy (CP) have various motor impairments, but less is known about the processing deficits of the somatosensory afference, especially in the proprioceptive domain. Proprioception (“the movement sense”) is behaviorally impaired primarily in the more affected hand of children with CP1,2 and bilaterally in the lower limbs2 . There are no prior studies quantifying the cortical proprioceptive processing in CP, but hand representation area is diminished to tactile stimuli in hemiplegic CP3 and the primary cortical response to tibial nerve stimulation is reduced in diplegic CP4nonPeerReviewe