Neuromagnetic studies on cortical somatosensory functions in infants and children : Normal development and effect of early brain lesions

Until recently, objective investigation of the functional development of the human brain in vivo was challenged by the lack of noninvasive research methods. Consequently, fairly little is known about cortical processing of sensory information even in healthy infants and children. Furthermore, mechanisms by which early brain insults affect brain development and function are poorly understood. In this thesis, we used magnetoencephalography (MEG) to investigate development of cortical somatosensory functions in healthy infants, very premature infants at risk for neurological disorders, and adolescents with hemiplegic cerebral palsy (CP). In newborns, stimulation of the hand activated both the contralateral primary (SIc) and secondary somatosensory cortices (SIIc). The activation patterns differed from those of adults, however. Some of the earliest SIc responses, constantly present in adults, were completely lacking in newborns and the effect of sleep stage on SIIc responses differed. These discrepancies between newborns and adults reflect the still developmental stage of the newborns’ somatosensory system. Its further maturation was demonstrated by a systematic transformation of the SIc response pattern with age. The main early adult­like components were present by age two. In very preterm infants, at term age, the SIc and SIIc were activated at similar latencies as in healthy fullterm newborns, but the SIc activity was weaker in the preterm group. The SIIc response was absent in four out of the six infants with brain lesions of the underlying hemisphere. Determining the prognostic value of this finding remains a subject for future studies, however. In the CP adolescents with pure subcortical lesions, contrasting their unilateral symptoms, the SIc responses of both hemispheres differed from those of controls: For example the distance between SIc representation areas for digits II and V was shorter bilaterally. In four of the five CP patients with cortico­subcortical brain lesions, no normal early SIc responses were evoked by stimulation of the palsied hand. The varying differences in neuronal functions, underlying the common clinical symptoms, call for investigation of more precisely designed rehabilitation strategies resting on knowledge about individual functional alterations in the sensorimotor networks.Lääketieteellisen teknologian kehitys on vasta viime vuosina mahdollistanut lasten aivotoiminnan tarkan, objektiivisen tutkimuksen. Näin ollen esimerkiksi aistiärsykkeiden aivoprosessoinnista vastasyntyneillä tiedetään varsin vähän, samoin kuin monien aivotoimintojen kehittymisestä lapsen kasvaessa. Myös ymmärrys erilaisten aivovaurioiden vaikutuksesta kehittyviin aivoihin on puutteellista. Magnetoenkefalografialla (MEG) tutkitaan aivohermosolujen toimintaa mittaamalla niissä syntyvien sähkövirtojen tuottamia magneettikenttiä pään ulkopuolelta. Väitöskirjassa MEG:n avulla tutkittiin tuntoaivokuoren toimintaa vastasyntyneillä ja tämän toiminnan kehitystä ensimmäisten elinvuosien aikana. Lisäksi tuntoaivokuoren toimintaa tarkasteltiin pikkukeskosena syntyneillä vauvoilla sekä nuorilla, joilla on varhaisen aivovaurion aiheuttama toispuoleinen CP-vamma. Jo vastasyntyneellä useat aivoalueet aktivoituivat käden alueen kosketusärsykkeen jälkeen. Tuntoaivokuoren aktiivisuus poikkesi kuitenkin oleellisesti aikuisesta: tietyt aikuistyyppiset aivovasteet puuttuivat vastasyntyneiltä täysin heijastaen vastasyntyneen vauvan hermoston keskeneräistä kehitysvaihetta. Tuntoaivovasteet kehittyivät iän myötä järjestelmällisesti siten, että kaksivuotiailla ne alkoivat morfologisesti muistuttaa aikuisten vasteita. Pikkukeskosten primaarisen tuntoaivokuoren vaste oli lasketussa ajassa heikompi kuin terveillä täysaikaisilla vauvoilla, mikä voi johtua pienemmästä aktivoituneesta hermosolujoukosta tai aktivaation epäsynkroniasta. Sekundaarisen tuntoaivokuoren vasteen puuttuminen liittyi poikkeaviin ultraääni- ja magneettikuvauslöydöksiin. Tämän havainnon ennusteellista merkitystä selvitetään parhaillaan seurantatutkimuksella. CP-vammaisilla nuorilla tuntoaivovasteissa havaittiin verrokkeihin nähden useita poikkeavuuksia, jotka olivat osin laaja-alaisempia kuin oli pääteltävissä kliinisistä oireista tai aivojen rakenteellisesta vauriosta. Esimerkiksi potilailla, joiden sairauden taustalla oli subkortikaalinen aivovaurio, etu- ja pikkusormien edustusalueet tuntoaivokuorella olivat verrokkeihin nähden lähempänä toisiaan sekä vaurion puoleisessa että vastakkaisessa aivopuoliskossa. Aivojen erilaisten rakenteellisten vaurioiden aiheuttamien toiminnallisten muutosten tarkempi ymmärtäminen voi osoittautua merkittäväksi CP-potilaiden kuntoutuksen ja hoidon yksilöllisessä räätälöinnissä

Spatial aspects of the dioxin risk formation in the Baltic Sea: A systematic review

Dioxins have been an inconvenience to the Baltic Sea ecosystem for decades. Although the concentrations in the environment and biota have continuously decreased, dioxins still pose a risk to human health. The risk and its formation vary in different parts of the Baltic Sea, due to variability in the environmental and societal factors affecting it. This paper presents a systematic literature review and knowledge synthesis about the regional dioxin risk formation in four sub-areas of the Baltic Sea and evaluates, whether systemic approach changes our thinking about the risk and its effective management. We studied the dioxin flux from atmospheric deposition to the Baltic Sea food webs, accumulation to two commercially and culturally important fish species, Baltic herring (Clupea harengus membras) and Baltic salmon (Salmo salar), and further to risk group members of four Baltic countries. Based on 46 studies, we identified 20 quantifiable variables and indexed them for commensurable regional comparison. Spatial differences in dioxin pollution, environmental conditions, food web dynamics, and the following dioxin concentrations in herring and salmon, together with fishing and fish consumption, affect how the final health risk builds up. In the southern Baltic Sea, atmospheric pollution levels are relatively high and environmental processes to decrease bioavailability of dioxins unfavorable, but the growth is fast, which curb the bioaccumu-lation of dioxins in the biota. In the North, long-range atmospheric pollution is minor compared to South, but the local pollution and slower growth leads to higher bioaccumulation rates. However, based on our results, the most remarkable differences in the dioxin risk formation between the areas arise from the social sphere: the emissions, origin of national catches, and cultural differences in fish consumption. The article suggests that acknowledging spatial characteristics of socio-ecological systems that generate environmental risks may aid to direct local focus in risk management.Peer reviewe

Cortical responses to tactile stimuli in preterm infants

Abstract The conventional assessment of preterm somatosensory functions using averaged cortical responses to electrical stimulation ignores the characteristic components of preterm somatosensory evoked responses (SERs). Our study aimed to systematically evaluate the occurrence and development of SERs after tactile stimulus in preterm infants. We analysed SERs performed during 45 electroencephalograms (EEGs) from 29 infants at the mean post-menstrual age of 30.7 weeks. Altogether 2,087 SERs were identified visually at single trial level from unfiltered signals capturing also their slowest components. We observed salient SERs with a high amplitude slow component at a high success rate after hand (95%) and foot (83%) stimuli. There was a clear developmental change in both the slow wave and the higher frequency components of the SERs. Infants with intraventricular haemorrhage (IVH; eleven infants) had initially normal SERs, but those with bilateral IVH later showed a developmental decrease in the ipsilateral SER occurrence after 30 weeks of post-menstrual age. Our study shows that tactile stimulus applied at bedside elicits salient SERs with a large slow component and an overriding fast oscillation, which are specific to the preterm period. Prior experimental research indicates that such SERs allow studying both subplate and cortical functions. Our present findings further suggest that they might offer a window to the emergence of neurodevelopmental sequalae after major structural brain lesions and, hence, an additional tool for both research and clinical neurophysiological evaluation of infants before term age.Peer reviewe

Sleep State Trend (SST), a bedside measure of neonatal sleep state fluctuations based on single EEG channels

Objective To develop and validate an automated method for bedside monitoring of sleep state fluctuations in neonatal intensive care units. Methods A deep learning-based algorithm was designed and trained using 53 EEG recordings from a long-term (a)EEG monitoring in 30 near-term neonates. The results were validated using an external dataset from 30 polysomnography recordings. In addition to training and validating a single EEG channel quiet sleep, we constructed Sleep State Trend (SST), a bedside-ready means for visualising classifier outputs. Results The accuracy of quiet sleep detection in the training data was 90%, and the accuracy was comparable (85-86 %) in all bipolar derivations available from the 4-electrode recordings. The algorithm generalised well to an external dataset, showing 81% overall accuracy despite different signal derivations. SST allowed an intuitive, clear visualisation of the classifier output. Conclusions Fluctuations in sleep states can be detected at high fidelity from a single EEG channel, and the results can be visualised as a transparent and intuitive trend in the bedside monitors. Significance The Sleep State Trend (SST) may provide caregivers a real-time view of sleep state fluctuations and its cyclicity.Peer reviewe

Forest condition monitoring under the UN/ECE and EU programmes in Finland

Part of the online report: Merilä, P. & Jortikka, S. (eds.). Forest Condition Monitoring in Finland – National report. The Finnish Forest Research Institute. http://urn.fi/URN:NBN:fi:metla-201305087568. Original webpages have been converted to a PDF file

Validating an SVM-based neonatal seizure detection algorithm for generalizability, non-inferiority and clinical efficacy

Neonatal seizure detection algorithms (SDA) are approaching the benchmark of human expert annotation. Measures of algorithm generalizability and non-inferiority as well as measures of clinical efficacy are needed to assess the full scope of neonatal SDA performance. We validated our neonatal SDA on an independent data set of 28 neonates. Generalizability was tested by comparing the performance of the original training set (cross -validation) to its performance on the validation set. Non-inferiority was tested by assessing inter-observer agreement between combinations of SDA and two human expert annotations. Clinical efficacy was tested by comparing how the SDA and human experts quantified seizure burden and identified clinically significant periods of seizure activity in the EEG. Algorithm performance was consistent between training and validation sets with no significant worsening in AUC (p > 0.05, n = 28). SDA output was inferior to the annotation of the human expert, however, re-training with an increased diversity of data resulted in non-inferior performance (delta kappa = 0.077, 95% CI:-0.002-0.232, n = 18). The SDA assessment of seizure burden had an accuracy ranging from 89 to 93%, and 87% for identifying periods of clinical interest. The proposed SDA is approaching human equivalence and provides a clinically relevant interpretation of the EEG.Peer reviewe

Menetelmän kehittäminen sosiaalihuollon toimintaprosessien kuvaamiseen

Sosiaalihuollon tietoteknologiahankkeessa (Tikesos) kehitetään sosiaalihuollon asiakastietojärjestelmiä sosiaalialan tietotarpeisiin vastaaviksi ja teknisesti yhteensopiviksi. Tämän saavuttamiseksi asiakastietojärjestelmiin liittyvät tiedot, asiakasasiakirjat ja toimintatavat on mallinnettava. Tässä artikkelissa kuvataan kehitteillä oleva menetelmä sosiaalihuollon toimintaprosessien mallintamiseen. Mallintamista tehdään QPR ProcessGuide ‐ohjelmistolla, JHS 152 ‐suositusten sekä BPMN‐määritysten mukaisesti. Toimintaprosessien mallintamista tehdään yhteistyössä sosiaalihuollon sisällön asiantuntijoiden sekä tietomäärityksiä ja teknisiä määrityksiä tekevien toimijoiden kanssa. Haasteita mallintamistyöhön tuovat sopivan kuvaustason löytäminen sekä sosiaalihuollon palveluiden monimuotoisuus

Development of human somatosensory cortical functions - what have we learned from magnetoencephalography: a review

Peer reviewe

Towards multimodal brain monitoring in asphyxiated newborns with amplitude-integrated EEG and simultaneous somatosensory evoked potentials

Background: Somatosensory evoked potentials (SEPs) offer an additional bedside tool for outcome prediction after perinatal asphyxia. Aims: To assess the reliability of SEPs recorded with bifrontoparietal amplitude-integrated electroencephalography (aEEG) brain monitoring setup for outcome prediction in asphyxiated newborns undergoing therapeutic hypothermia. Study design: Retrospective observational single-center study. Subjects: 27 consecutive asphyxiated fullor near-term newborns (25 under hypothermia) that underwent median nerve aEEG-SEPs as part of their clinical evaluation at the neonatal intensive care unit of Helsinki University Hospital. Outcome measures: aEEG-SEP classification (present, absent or unreliable) was compared to classification of SEPs recorded with a full EEG montage (EEG-SEP), and outcome determined from medical records at approximately 12-months-age. Unfavorable outcome included death, cerebral palsy, or severe epilepsy. Results: The aEEG-SEP and EEG-SEP classifications were concordant in 21 of the 22 newborns with both recordings available. All five newborns with bilaterally absent aEEG-SEPs had absent EEG-SEPs and the four with outcome information available had an unfavorable outcome (one was lost to follow-up). Of the newborns with aEEG-SEPs present, all with follow-up exams available had bilaterally present EEG-SEPs and a favorable outcome (one was lost to follow-up). One newborn with unilaterally absent aEEG-SEP at 25 h of age had bilaterally present EEG-SEPs on the next day, and a favorable outcome. Conclusions: aEEG-SEPs recorded during therapeutic hypothermia on the first postnatal days are reliable for assessing brain injury severity. Adding SEP into routine aEEG brain monitoring offers an additional tool for very early outcome prediction after birth asphyxia.Peer reviewe

Lasten kliinisen neurofysiologian tutkimuskäytännöt

VertaisarvioituKliinisen neurofysiologian menetelmillä selvitetään keskus- ja ääreishermoston sekä lihaksiston sairauksia. Lapsilla yleisin tutkimus on aivosähkökäyrä eli EEG, jolla selvitetään erityisesti kohtausoireiden taustaa. Tavallisia ovat myös uni- ja vireystilatutkimukset, elektroneuromyografia ja herätevastetutkimukset. Erityistilanteissa tarvitaan akuuttihoidon aivomonitorointia, leikkauksenaikaista neuromonitorointia sekä aivotoimintojen paikantamista.Peer reviewe