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ObjectivesTo assess neurocognitive function in adults born with low birthweight compared with controls and to explore associations between neurocognitive function and psychopathology in these groups.MethodsIn this prospective cohort study, one group born preterm with very low birthweight (VLBW: birthweight g, n = 53), one group born small for gestational age at term (SGA: birthweight n = 63) and one term-born control group (birthweight ≥10th percentile, n = 81) were assessed with neurocognitive tests, diagnostic interviews, and self-report questionnaires at 26 years of age.ResultsThe VLBW group scored significantly below the control group on several neurocognitive measures, including IQ measures, psychomotor speed, verbal fluency, aspects of visual learning and memory, attention, social cognition, working memory and fine motor speed. The SGA group consistently scored at an intermediate level between the VLBW and the control group and had significantly lower scores than controls on Performance IQ and psychomotor speed, including switching. In the VLBW group, associations were found between lower spatial working memory and the presence of anxiety disorders, internalizing and attention problems, and autistic traits. Furthermore, lower Full scale IQ was associated with attention problems when adjusting for sex and parental socioeconomic status.ConclusionAdults born preterm with VLBW or born term SGA displayed neurocognitive difficulties. Spatial working memory was associated with difficulties with attention, anxiety, and social function of VLBW adults. The finding and its clinical applicability should be further explored.

BackgroundAdaptive computerized working memory (WM) training has shown favorable effects on cerebral cortical thickness as compared to non-adaptive training in healthy individuals. However, knowledge of WM training-related morphological changes in mild cognitive impairment (MCI) is limited.ObjectiveThe primary objective of this double-blind randomized study was to investigate differences in longitudinal cortical thickness trajectories after adaptive and non-adaptive WM training in patients with MCI. We also investigated the genotype effects on cortical thickness trajectories after WM training combining these two training groups using longitudinal structural magnetic resonance imaging (MRI) analysis in Freesurfer.MethodMagnetic resonance imaging acquisition at 1.5 T were performed at baseline, and after four- and 16-weeks post training. A total of 81 individuals with MCI accepted invitations to undergo 25 training sessions over 5 weeks. Longitudinal Linear Mixed effect models investigated the effect of adaptive vs. non-adaptive WM training. The LME model was fitted for each location (vertex). On all statistical analyzes, a threshold was applied to yield an expected false discovery rate (FDR) of 5%. A secondary LME model investigated the effects of LMX1A and APOE-ε4 on cortical thickness trajectories after WM training.ResultsA total of 62 participants/patients completed the 25 training sessions. Structural MRI showed no group difference between the two training regimes in our MCI patients, contrary to previous reports in cognitively healthy adults. No significant structural cortical changes were found after training, regardless of training type, across all participants. However, LMX1A-AA carriers displayed increased cortical thickness trajectories or lack of decrease in two regions post-training compared to those with LMX1A-GG/GA. No training or training type effects were found in relation to the APOE-ε4 gene variants.ConclusionThe MCI patients in our study, did not have improved cortical thickness after WM training with either adaptive or non-adaptive training. These results were derived from a heterogeneous population of MCI participants. The lack of changes in the cortical thickness trajectory after WM training may also suggest the lack of atrophy during this follow-up period. Our promising results of increased cortical thickness trajectory, suggesting greater neuroplasticity, in those with LMX1A-AA genotype need to be validated in future trials.

Preterm birth with very low birth weight (VLBW) confers heightened risk for perinatal brain injury and long-term cognitive deficits, including a reduction in IQ of up to one standard deviation. Persisting gray and white matter aberrations have been documented well into adolescence and adulthood in preterm born individuals. What has not been documented so far is a plausible causal link between reductions in cortical surface area or subcortical brain structure volumes, and the observed reduction in IQ. The NTNU Low Birth Weight in a Lifetime Perspective study is a prospective longitudinal cohort study, including a preterm born VLBW group (birthweight ≤1500 g) and a term born control group. Structural magnetic resonance imaging data were obtained from 38 participants aged 19, born preterm with VLBW, and 59 term-born peers. The FreeSurfer software suite was used to obtain measures of cortical thickness, cortical surface area, and subcortical brain structure volumes. Cognitive ability was estimated using the Wechsler Adult Intelligence Scale, 3rd Edition, including four IQ-indices: Verbal comprehension, Working memory, Perceptual organization, and Processing speed. Statistical mediation analyses were employed to test for indirect effects of preterm birth with VLBW on IQ, mediated by atypical brain structure. The mediation analyses revealed negative effects of preterm birth with VLBW on IQ that were partially mediated by reduced surface area in multiple regions of frontal, temporal, parietal and insular cortex, and by reductions in several subcortical brain structure volumes. The analyses did not yield sufficient evidence of mediation effects of cortical thickness on IQ. This is, to our knowledge, the first time a plausible causal relationship has been established between regional cortical area reductions, as well as reductions in specific subcortical and cerebellar structures, and general cognitive ability in preterm born survivors with VLBW.

Objective We aimed to evaluate the effectiveness of an adaptive working memory (WM) training (WMT) program, the corresponding neural correlates, and LMX1A‐rs4657412 polymorphism on the adaptive WMT, in human immunodeficiency virus (HIV) participants compared to seronegative (SN) controls. Methods A total of 201 of 206 qualified participants completed baseline assessments before randomization to 25 sessions of adaptive WMT or nonadaptive WMT. A total of 74 of 76 (34 HIV, 42 SN) completed adaptive WMT and all 40 completed nonadaptive WMT (20 HIV, 20 SN) and were assessed after 1 month, and 55 adaptive WMT participants were also assessed after 6 months. Nontrained near‐transfer WM tests (Digit‐Span, Spatial‐Span), self‐reported executive functioning, and functional magnetic resonance images during 1‐back and 2‐back tasks were performed at baseline and each follow‐up visit, and LMX1A‐rs4657412 was genotyped in all participants. Results Although HIV participants had slightly lower cognitive performance and start index than SN at baseline, both groups improved on improvement index (>30%; false discovery rate [FDR] corrected p

Table S1. Non-participant characteristics. Table S2. Descriptive values of Autism-Spectrum Quotient excluding participants with IQ < 85 at 19 years. Table S3. Confounder analysis: Linear regression coefficients with ASEBA ASR Total Problems score, AQ sum score and PDI Grand Total Score as dependent variables in the preterm VLBW group vs the control group, adjusted separately for each variable. Table S4. Confounder analysis: Linear regression coefficients with ASEBA ASR Total Problems score, AQ sum score and PDI Grand Total Score as dependent variables in the term SGA group vs the control group, adjusted separately for each variable. Table S5. Perinatal risk factors and neurodevelopmental markers in the preterm VLBW group excluding three participants with CP; linear regression with ASEBA ASR Total Problems score, AQ Sum score and PDI Grand Total score separately as dependent variables, and for each variable one at a time as covariate. (DOCX 41 kb)

Children born prematurely with very low birth weight (VLBW: bw ≤ 1500 g) have an increased risk of preterm perinatal brain injury, which may subsequently alter the maturation of the brain, including the cerebral cortex. The aim of study was to assess cortical thickness and surface area in VLBW children compared with term-born controls, and to investigate possible relationships between cortical morphology and Full IQ. In this cross-sectional study, 37 VLBW and 104 term children born between the years 2003–2007 were assessed cognitively at 5–10 years of age, using age appropriate Wechsler tests. The FreeSurfer software was used to obtain estimates of cortical thickness and surface area based on T1-weighted MRI images at 1.5 Tesla. The VLBW children had smaller cortical surface area bilaterally in the frontal, temporal, and parietal lobes. A thicker cortex in the frontal and occipital regions and a thinner cortex in posterior parietal areas were observed in the VLBW group. There were significant differences in Full IQ between groups (VLBW M = 98, SD = 9.71; controls M = 108, SD = 13.57; p

Appendix 2B. Brain growth differences between the two VLBW diagnostic groups and the control group from 15 to 19 years of age corrected for IQ. There were no differences in GM volume growth rate in the brain cortex, thalamus and subcortical GM between the two VLBW subgroups and controls. (DOCX 13 kb)

Appendix 4A. Mixed linear regressions with psychiatric data as dependent variable and brain volumes (ml) and time as independent variables in the VLBW group. Adjusted for sex and total intracranial volume, but not for IQ. There were no associations between GM volume growth rate in the brain cortex, thalamus or in subcortical GM and CGAS scores in the VLBW group. (DOCX 19 kb)

Appendix 1A. Brain volume (ml) differences between the two VLBW diagnostic groups and controls at 15 and 19 years of age. The two VLBW groups tended to have smaller brain volumes than the controls in all studied areas. Subcortical gray matter, was in the persisting/developing diagnosis VLBW group smaller than in both controls and the healthy/becoming healthy VLBW group. (DOCX 23 kb)

Appendix 3B. Relationship between brain volumes and psychiatric symptoms assessed with questionnaires in the VLBW group at 15 and 19 years of age corrected for IQ. Occipital and parietal cortex volumes predicted lower scores in general psychosocial functioning at 15 years. Smaller volumes of occipital and parietal cortex predicted higher hyperactivity scores at 15 years. (DOCX 23 kb)

Appendix 2A. Brain growth differences between the two VLBW subgroups and the control group from 15 to 19 years of age. There were no differences in GM volume growth rate in the brain cortex, thalamus and subcortical GM between the two VLBW subgroups and controls. (DOCX 13 kb)

Appendix 3A. Relationship between brain volumes and psychiatric symptoms assessed with questionnaires in the VLBW group at 15 and 19 years of age. At 15 years of age, smaller volumes of occipital and parietal cortex and of thalamus predicted lower scores in general psychosocial functioning (CGAS scores). Smaller subcortical GM volumes predicted lower psychosocial functioning at both 15 and 19 years. Smaller volumes of occipital and parietal cortex predicted higher inattention scores in at both ages, although not all differences survived corrections for multiple comparisons. (DOCX 16 kb)

Appendix 4B. Mixed linear regressions with psychiatric data as dependent variable and brain volumes (ml) and time as independent variables in the VLBW group. Adjusted for sex, total intracranial volume and IQ. There were no associations between GM volume growth rate in the brain cortex, thalamus or in subcortical GM and CGAS scores in the VLBW group. (DOCX 18 kb)

Appendix 1B. Brain volume (ml) differences between the two VLBW diagnostic groups and controls at 15 and 19 years of age corrected for IQ. Both VLBW subgroups had persistent smaller volume of parietal cortex than controls at both time points. The healthy/becoming healthy VLBW subgroup had smaller cingulate and temporal volumes at both ages and smaller frontal cortical volume at 19 years than the control group. Thalamic volumes were smaller in the VLBW subgroup with persisting/developing diagnosis than in controls at both ages. (DOCX 22 kb)

Mild cognitive impairment (MCI) is a condition characterized by memory problems that are more severe than the normal cognitive changes due to aging, but less severe than dementia. Reduced working memory (WM) is regarded as one of the core symptoms of an MCI condition. Recent studies have indicated that WM can be improved through computer-based training. The objective of this study is to evaluate if WM training is effective in improving cognitive function in elderly patients with MCI, and if cognitive training induces structural changes in the white and gray matter of the brain, as assessed by structural MRI.The proposed study is a blinded, randomized, controlled trail that will include 90 elderly patients diagnosed with MCI at a hospital-based memory clinic. The participants will be randomized to either a training program or a placebo version of the program. The intervention is computerized WM training performed for 45 minutes of 25 sessions over 5 weeks. The placebo version is identical in duration but is non-adaptive in the difficulty level of the tasks. Neuropsychological assessment and structural MRI will be performed before and 1 month after training, and at a 5-month folllow-up.If computer-based training results in positive changes to memory functions in patients with MCI this may represent a new, cost-effective treatment for MCI. Secondly, evaluation of any training-induced structural changes to gray or white matter will improve the current understanding of the mechanisms behind effective cognitive interventions in patients with MCI.ClinicalTrials.gov NCT01991405. November 18, 2013.

Additional file 1: Appendix S1. Mixed model linear regressions with psychiatric data as dependent variable and cerebellar volumes (ml) and time as independent variables in the VLBW group. Adjusted for age, gender and estimated intracranial volume, but not for IQ.

Additional file 3: Appendix S3. Linear regression with psychiatric data as dependent variable and cerebellar volumes (ml) as independent variable in the VLBW group adjusted for IQ.

Additional file 2: Appendix S2A. Cerebellar volume (ml) differences between the two VLBW diagnostic groups and controls at 15 and 19 years of age. B. Cerebellar volume (ml) differences between the two VLBW diagnostic groups and controls at 15 and 19 years of age adjusted for IQ.

Proportion (%) of young people living with their parents in New Zealand, 1981–2006. (DOCX 14 kb)

Nasjonalt kunnskapssenter for helsetjenesten fikk i oppdrag fra Helsedirektoratet å lage en systematisk kunnskapsoppsummering om effekten av intensiv trening/habilitering av barn med medfødt og ervervet hjerneskade. Intensive training/habilitation for children with brain damage

Being born preterm (< 37 gestational weeks) and especially preterm with very low birth weight (< 1500 grams) has been shown to associate with adverse health outcomes in adolescence and adulthood: higher blood pressure, elevated glucose levels, and lower bone mineral density. Being born very preterm at very low birth weight has been associated with smaller brain volumes. It is still unclear, however, how the extreme stress of preterm birth manifests in adulthood. Nearly all studies have been conducted with unrelated controls, leaving room for residual confounding that a sibling comparison may address. In my dissertational thesis I investigate how adults born preterm at very low birth weight differ from their term born siblings in regard to brain, bone, and abdominal adipose tissue pools. In addition to this, I aim to identify epigenetic imprints of preterm birth from adult leukocyte DNA from individuals born preterm at very low birth weight, which could reflect a permanent change in gene activity regulation. I discovered that adults born at very low birth weight have more incidental findings than their term siblings in brain MRI, smaller total brain volume, less gray matter, smaller basal ganglia and larger ventricles than their siblings. Contrary to earlier studies, there was no difference in white matter volume. I discovered that adults born preterm at very low birth weight have a lower bone mineral density in the femoral neck, and additionally whole body bone mineral content was lower in those born at very low birth weight. The differences between groups, however, attenuated after taking body mass index and height into account in statistical modelling. Regarding fat outcomes, no differences in adipose tissue volumes or hepatic fat were observed. There was, however, less unsaturation in magnetic resonance spectroscopy of subcutaneous abdominal adipose tissue, which may be related to reported differences in resting state energy expenditure or fatty acid metabolism. I discovered differences in the methylation of several genes and further aimed to validate these findings in independent cohorts. By combining results from said cohorts, I discovered five sites in the epigenome that seem to be associated with both birth weight and being born preterm at very low birth weight. Being born preterm, very preterm or with a very low birth weight is a major factor contributing to adult health, which, based on my dissertational thesis and sibling comparison, has lasting effects well into adulthood. In particular, my thesis contributes to the understanding of brain volume differences and high prevalence of incidental findings as well as bone and adipose tissue differences and similarities between adults born at very low birth weight and term siblings. Keskosuuden (< 37 täyttä raskausviikkoa) ja etenkin pikkukeskosuuden (alle 1500 gramman syntymäpaino) on osoitettu olevan yhteydessä aikuisiällä korkeampaan lepoverenpaineeseen, kohonneeseen paastoverensokeriin, huonompaan keuhkojen toimintaan ja pienempään luuntiheyteen. Pikkukeskosuuden on myös raportoitu olevan yhteydessä pienempään aivotilavuuteen. Toistaiseksi on epäselvää, miten pikkukeskosena syntymisen stressi ilmenee aikuisuudessa. Miltei kaikki aiemmat tutkimukset on suoritettu keskenään sukua olemattomia henkilöitä vertaamalla, minkä valossa sisarusvertailu huomioi paremmin mahdolliset sekoittavat tekijät tulosten tulkinnassa. Väitöstutkimuksessani pyrin selvittämään miten aivot, luuntiheys sekä vatsan alueen rasvat eroavat pikkukeskosena syntyneiden tutkittavien ja heidän täysiaikaisena syntyneiden sisarustensa välillä. Tämän lisäksi pyrin tunnistamaan pikkukeskosena syntyneiltä valkosolujen DNA:sta epigeneettisiä muutoksia, jotka voisivat merkitä pysyvää keskosuuden jättämää jälkeä perimän säätelyssä. Havaitsin, että pikkukeskosena syntyneillä on enemmän sattumalöydöksiä kuin sisaruksilla, mutta ne ovat luonteeltaan pääsääntöisesti kliinisesti merkityksettömiä. Pikkukeskosena syntyneillä oli pienempi aivojen kokonaistilavuus, vähemmän harmaata ainetta pienemmät tyvitumakkeet ja suuremmat aivokammiot kuin sisaruksilla. Sen sijaan valkean aineen määrässä en havainnut eroa. Pikkukeskosena syntyminen oli yhteydessä alhaisempaan luuntiheyteen reisiluun kaulassa, ja lisäksi koko kehon luuston mineraalipitoisuus oli alhaisempaa. Kun otin huomioon tutkittavien painoindeksin ja pituuden, ryhmien välillä ei ollut tilastollisesti merkitseviä eroja. En havainnut eroa vatsan alueen rasvakudoksen tilavuuksissa, eikä maksan rasvan määrässäkään ollut havaittavaa eroa, mutta ihonalaisrasvassa oli vähemmän kaksoissidossignaalia magneettiresonanssispektroskopiassa. Tämä voi olla merkki eroista lepoaineenvaihdunnassa tai rasvametaboliassa. Viimeisessä osatyössäni havaitsin eroja useiden geenien metylaatiossa, ja pyrin toistamaan löydöksen useissa eri-ikäisissä kohorteissa. Yhdistämällä eri kohorttien tuloksia löysin viisi geenialuetta, jotka näyttävät yhdistyvän pikkukeskosuuteen ja alhaiseen syntymäpainoon. Pikkukeskosena syntyminen on erityinen aikuisiän terveyteen ja hyvinvointiin yhteydessä oleva tekijä, jonka merkitys säilyy väitöskirjatyöni sisarusvertailun perusteella vielä pitkälle aikuisuuteen. Väitöskirjani tulokset auttavat ymmärtämään pikkukeskosena syntymisen yhteyttä aikuisiän aivotilavuuksiin ja sattumalöydöksiin sekä luuston ja rasvan eroihin suhteessa täysiaikaisiin sisarusverrokkeihin.

ENGLISH - Brain development, connectivity, and cognition following preterm birth with very low birthweight: Preterm birth (

LANGTIDSKONSEKVENSER AV FOR TIDLIG FØDSEL Motoriske ferdigheter, psykisk helse, livskvalitet og integritet av hjernens hvite substans hos unge voksne født for tidlig med veldig lav fødselsvekt Barn som er født for tidlig har umodne organer som er mer utsatt for skade enn barn født til termin. Hjernen er spesielt sårbar, og diffus skade av hvit substans forekommer hyppig. Risikoen for død og sykelighet øker med lavere fødselsvekt og gestasjonsalder. Barn født med veldig lav fødselsvekt (VLBW;≤1500g) har økt forekomst av vansker med motorikk, kognisjon, atferd, oppmerksomhet og læring. Flere har sosiale utfordringer, og psykiske symptomer og plager blir mer fremtredende i tenårene. I voksen alder er det færre som tar høyere utdanning, har fast partner og lever et selvstendig liv. Det er tidkrevende og kostbart å studere langtidseffektene av VLBW, og få studier har fulgt denne gruppen inn i voksen alder. Dette doktorgradsarbeidet er en del av et større hovedprosjekt, Lav fødselsvekt i et livstidsperspektiv, ved Senter for tidlig hjerneutvikling (CEBRA). I dette prosjektet har vi fulgt for tidlig fødte barn med VLBW og terminfødte barn med fødselsvekt ≥10-persentilen fra fødsel og inn i voksen alder. Disse gruppene har blitt undersøkt på flere tidspunkt med mange ulike tester, spørreskjema og MR av hjernen. I denne avhandlingen undersøkte vi motoriske ferdigheter, psykisk helse, livskvalitet og integritet av hjernens hvite substans ved 23 års alder. Vi undersøkte også utviklingen av motoriske ferdigheter fra 14 til 23 år og studerte potensielle endringer i psykisk helse og livskvalitet i overgangen til selvstendig voksenliv fra 20 til 23 års alder. Dessuten undersøkte vi om motoriske ferdigheter kunne være relatert til psykisk helse og livskvalitet, og om motoriske problemer kunne henge sammen med endringer i hvit substans. Vi fant at VLBW-gruppen hadde dårligere fin- og grovmotoriske ferdigheter ved 23 år sammenlignet med kontrollgruppen, særlig på oppgaver som krevde motorisk hurtighet. Det var ingen forbedring av motoriske ferdigheter fra 14 til 23 år. Hovedforskjellene bestod da vi ekskluderte deltakere med cerebral parese. VLBW-gruppen rapporterte dårligere psykisk helse enn kontrollgruppen ved 23 år i form av mer oppmerksomhets- og internaliserende problemer, samt en tendens til flere symptomer på angst heller enn depresjon. Det var en økning i psykiske plager fra 20 til 23 år i VLBW-gruppen. Ved 23 år hadde de også en tendens til å rapportere færre og svakere sosiale relasjoner, men et lavere alkoholforbruk enn kontrollgruppen. Videre rapporterte VLBW-gruppen lavere fysisk og psykisk livskvalitet enn kontrollgruppen, inkludert redusert fysisk og sosial fungering som påvirket deres hverdagsroller, samt mer kroppslig smerte. Både fysisk og psykisk livskvalitet ble svekket fra 20 til 23 år i VLBW-gruppen. Reduserte motoriske ferdigheter var relatert til dårligere psykisk helse, mer internaliserende problemer og lavere fysisk og psykisk livskvalitet. Gruppeforskjellene for psykisk helse og livskvalitet ble mindre da vi ekskluderte deltakere med cerebral parese og lav IQ, men hovedforskjellene bestod og det var fremdeles en sammenheng mellom reduserte motoriske ferdigheter og lavere fysisk livskvalitet. I forhold til kontrollgruppen fant vi endringer i hvit substans i alle hjernens sentrale nervebaner hos VLBW-gruppen ved 23 år, og disse gruppeforskjellene syntes å øke i omfang fra 20 til 23 år. Reduserte motoriske ferdigheter var assosiert med endringer i hvit substans i motoriske nervebaner hos VLBW-gruppen ved 23 år. Vi konkluderte med at unge voksne født med VLBW ikke vokser av seg motoriske problemer og at de rapporterer dårligere og synkende psykisk helse og livskvalitet inn i ung voksen alder sammenlignet med kontrollgruppen. De har fortsatt synlige og mulig økende endringer i hvit substans, og disse endringene var assosiert med reduserte motoriske ferdigheter. Disse funnene indikerer at endringer i hvit substans kan påvirke funksjonen hos unge voksne født med VLBW og at overgangen til voksenlivet synes å være spesielt utfordrende for denne gruppen.

Mange barn med cerebral parese har vansker med å utføre daglige aktiviteter i hjem, skole eller barnehage på grunn av nedsatt håndfunksjon Til tross for det store omfanget av slike vansker, så er behandlingen som tilbys for å bedre håndfunksjonen i liten grad kunnskapsbasert. Dette gjelder spesielt behandling for å bedre håndfunksjonen hos barn med nedsatt funksjon i begge hender (bilateral CP). Hovedårsaken til dette er at man mangler gyldige og pålitelige måleredskaper som er følsomme nok til å måle endring. Funksjonelle klassifikasjoner og standardiserte tester med gode måleegenskaper er avgjørende for å kunne følge opp barnets naturlige utvikling og gi råd rundt forventet utvikling, samt for å kunne planlegge og evaluere aktuelle behandlingstilbud. De viktigste målene med denne avhandlingen er derfor (1) å undersøke gyldighet (validitet) og pålitelighet (reliabilitet) til en mye brukt klassifisering av finmotorikk hos barn med CP, og (2) å bidra til bedre planlegging og evaluering av aktuelle tiltak ved å identifisere og utvikle standardiserte håndfunksjonstester med gode måleegenskaper for barn med bilateral CP. Studie I og II undersøker validitet og reliabilitet av Bimanual Fine Motor Function (BFMF), som er en klassifisering av finmotorisk funksjon hos barn med CP. I studie I besto datasettet av BFMF og Manual Ability Classification System (MACS) klassifiseringer fra 539 barn med CP, mens i studie II ble 79 barn med CP inkludert. Studie III og IV undersøker måleegenskapene til standardiserte tester som evaluerer håndfunksjon hos barn med bilateral CP. Studie III er en systematisk litteraturgjennomgang som identifiserer tilgjengelige håndfunksjonstester og vurderer måleegenskapene til disse testene, mens studie IV beskriver utviklingen og valideringen av den nye testen, Both Hands Assessment (BoHA), der data fra 171 barn med bilateral CP ble benyttet. Resultatene indikerer at BFMF er en valid og reliabel klassifisering av finmotorisk kapasitet hos barn med CP. Ved bruk av både BFMF og MACS, som klassifiserer faktisk bruk av hendene, kan man få en mer utfyllende beskrivelse av barnets håndfunksjon. Gjennom den systematiske litteraturgjennomgangen identifiserte vi et foreldre-rapportert spørreskjema og fire håndfunksjonstester. Spørreskjemaet måler hvor lett eller vanskelig det er for barnet å utføre ulike daglige aktiviteter som krever bruk av hendene, men gir ingen informasjon om det er en eller begge hender som brukes. Tre av håndfunksjonstestene evaluerer kapasitet til å bruke hver hånd for seg, mens den fjerde hovedsakelig evaluerer om barnet har aldersadekvat funksjon i dominant hånd. Best evidens for validitet og reliabilitet ble funnet for spørreskjemaet ABILHAND-kids og for testen Melbourne Assessment 2, men informasjon om følsomhet for endring mangler for begge disse instrumentene. Vi identifiserte ingen håndfunksjonstester som på en valid og reliabel måte måler hvordan barn med bilateral CP håndterer gjenstander ved bruk av begge hender. Derfor utviklet og validerte vi en ny test, Both Hands Assessment (BoHA), for å måle tohåndsfunksjon hos barn med bilateral CP (MACS nivå I-III). Resultatet av dette viser at BoHA er en valid test for barn med bilateral CP når den deles inn i to versjoner; en for barn med asymmetrisk (BoHA-A) og en for barn med mer symmetrisk bruk av hendene (BoHA-S). Ankring av disse to versjonene til samme måleskala gjør at resultatene som oppnås kan sammenlignes uavhengig av om barnet har en asymmetrisk eller mer symmetrisk bruk av hendene. Denne avhandlingen viser at BFMF er en valid og reliabel klassifisering av finmotorisk funksjon hos barn med CP. Bruk av BFMF sammen med MACS vil kunne gi en mer nyansert beskrivelse av håndfunksjonen hos barn med CP, noe som er nyttig både i klinikk og forskning. For å kunne planlegge å måle effekt av ulike tiltak er det imidlertid behov for valide og reliable tester som er følsomme for endring. Melbourne Assessment 2 kan benyttes for å måle enhåndskapasitet hos barn med bilateral CP, mens ABILHAND-kids kan benyttes for å måle hvor lett eller vanskelig det er for barnet å utføre daglige aktiviteter som krever bruk av hendene. Det er imidlertid usikkert hvor godt disse måleinstrumentene fanger opp endring. Den nye testen BoHA gir en valid måling av spontan bruk av begge hender hos barn med bilateral CP og tilbyr dermed et nytt perspektiv som kan være nyttig ved planlegging og evaluering av tiltak. Fremtidige studier som undersøker reliabilitet og hvor godt BoHA fanger opp endring er imidlertid nødvendige.