A Study On Neonatal Brain Cognitive Characteristics And Early Auditory Stimulation Intervention By Electrophysiology Method

The neonatal period is a critical and sensitive time for brain development.Cognition is one of the higher brain functions,and the good cognitive state of the newborn lays a solid foundation for lifelong development.The early development of hearing makes auditory perception function the main manifestation of neonatal brain function.Neonates can recognize the sounds exposed to the fetus,recognize the mother’s voice,and have sensitive recognition ability to different frequency loudness and different emotions of sound stimulation,and have the initial performance of cognitive functions such as memory,attention,choice,learning and classification.However,newborn brain cognition is in the process of gradual development and improvement,with atypical functional expression,complex,unstable,immature and other characteristics,which are affected by many factors.It is not clear how to evaluate the cognitive development characteristics of normal newborns.In addition to intrauterine development,environmental factors after birth are very important,and early experience plays a pivotal role in brain cognitive development.In the process of fetal and neonatal delivery,it may face the interference of various high risk factors such as immature brain development,hypoxia and ischemia,intracranial infection,hemorrhage and so on.At the same time,the environment after birth is also an important factor affecting the brain cognitive development of neonates.Therefore,this stage of brain cognition is not mature,unstable.If disease is more complex and varied,how can we measure it scientifically?Neonatal brain has strong plasticity and neuroplasticity is a compensation mechanism for brain injury.Environment is a key factor affecting neuroplasticity.Favorable stimulation of external environment plays an important role in brain development and cognitive formation,and brain function and cognitive control can be exercised and optimized in the process of responding to enriched environment.So how can we implement environmental intervention and protection early in life using neuroplasticity?Studies have shown that the inevitable problems of sound,light,pain and separation from mother in the neonatal intensive care unit(NICU)are detrimental to the brain cognitive functions of newborn cognition,behavior and emotion.How to remedy these problems?It is necessary to have scientific research methods and evaluation means throughout for studying the basic physiological cognitive characteristics of the brain and the cognitive characteristics of the brain after brain injury,and for exploring new clinical early intervention schemes.There are many methods to study brain cognitive function,such as neuroelectrophysiological techniques(EEG,ERP),Brain structure imaging(CT,MRI),Functional brain imaging(PET,fMRI),Cognitive tests(scales,psychological tests,etc.).For the special population of neonates and even premature infants,it is non-invasive,safe and simple,sensitive and reproducible,and suitable for tracking at different age stages.EEG and event related potential(ERP)meet these requirements.EEG contains a variety of cortical activity information,which can reflect the information transmission and integration between neurons in the brain in real time.Resting state EEG(rs-EEG),which records brain activity when not performing cognitive tasks,is well suited to individuals throughout the life cycle and in atypical developmental populations.Auditory ERP is regarded as a scientific tool for detecting cognitive function in early life due to its high temporal resolution at the millisecond level,which can accurately depict the real-time state of brain activity without the active cooperation of subjects.Therefore,EEG and ERP are ideal scientific tools to study the cognitive function of newborn brain.Therefore,this study focuses on the above three problems and uses the brain cognitive research tools suitable for neonates to study the characteristics of the brain cognitive function of normal neonates firstly.Secondly,the cognitive characteristics of hypoxic ischemic encephalopathy(HIE)and the predictive indexes of neural development of high-risk neonates were explored.Thirdly,using the characteristics of early auditory development,the early auditory stimulation of asphyxia neonates was explored.Part Ⅰ Cognitive characteristics of normal neonatesIn this study,EEG and ERP techniques were used to study the brain cognitive function of normal neonates at different levels,and to explore the characteristics of normal neonates at different ages,genders,hemispheres and brain development levels.The study is explained from the following three parts:1.EEG study on brain cognitive function of normal neonatesObjective:To study the characteristics of cerebral cognitive function in developing normal neonates by EEG.Methods:100 full-term neonates in the neonatology department of our hospital or the outpatient department were randomly selected and divided into 1-10d group,11-20d group and 21-28d group according to the daily age.Perinatal brain injury was excluded,NBNA score ≥38,and both ears passed the hearing screening.The 32-guide Stellate digital paperless EEG from Canada was used.The recording electrode was placed according to the standard 10-20 system of international electroencephalogram Society.The whole experiment was recorded by video surveillance.The EEG in the resting state was recorded for 10-15 minutes,and then the sound stimulus was delivered,and the task-state EEG was collected synchronously.BESA 6.0 software was used for off-line analysis of EEG data.Fourier transform(FFT)was used to obtain EEG power values of each frequency band,and the power spectrum of δ wave in different states was measured.Results:(1)The comparison of EEG power in different states of neonates showed that the EEG power in Cz and Fz lead groups increased significantly compared with that in resting state,and the difference was statistically significant(P<0.05).(2)Comparison of EEG power of neonates at different ages:Fz and Cz leads,resting and task states showed that EEG power gradually increased from 1 to 10 days(group 1),peaked from 11 to 20 days(group 2),and gradually decreased from 21 to 28 days(group 3),with statistically significant changes(P<0.05).The above results can also be seen in the brain power map.Conclusion:8 wave EEG power of task state increased significantly compared with that of resting state.And 11-20 days after birth is an important period of auditory brain cognitive development.2.ERP study on auditory brain cognitive function of normal neonatesObjective:To study the characteristics of auditory brain cognitive function in developing normal neonates by ERP.Methods:110 full-term neonates in neonatology department of our hospital were randomly divided into 1-10d group,11-20d group and 21-28d group according to their daily age.Perinatal brain injury was excluded,NBNA score≥38,and both ears passed hearing screening.The classical Oddball paradigm was used to generate sound stimulation,and the Canadian 32-lead Stellate digital EEG was used to record EEG signals synchronously.BESA 6.0 and EEGLAB toolkit on MATLAB R2014b platform were used for offline analysis of EEG data.The characteristics of ERP were observed,and the latency and area of N2 wave were analyzed with age,sex and left and right cerebral hemispheres.Results:(1)The overall mean wave of ERP in neonates was broad and gentle.N2 wave showed a low flat composite wave with multiple peaks in the group of 1-10 days,while N2 wave showed a regular and high wave trend in the group of 11-20 days and 21-28 days,and gradually became a single wave.(2)With the increase of age,the area of N2 wave under Fz and Cz lead target stimulation increased gradually,and there were statistical differences among the three groups(P<0.05).The incubation period of N2 wave decreased significantly,and there were statistical differences among the three groups(P<0.05).The difference between the three groups showed that N2 area increased significantly and incubation period decreased significantly at 11-20 days(P<0.05).(3)The area of N2 wave in C3 lead was significantly larger than that in C4 lead,with statistical significance(P<0.05).The latency of N2 wave in C3 lead was significantly shorter than that in C4 lead(P<0.05).There were no statistical differences in the N2 wave area and latency of F3 and F4 leads(P>0.05).But there were statistically significant differences in the N2 wave area of F3 and F4 in infants at 29-60 days(P<0.05).(4)Fz and Cz lead neonates of different genders,N2 wave area of female neonates was significantly larger than that of male neonates(P<0.05),and the latency was significantly shorter than that of male neonates(P<0.05).Conclusion:With the increase of age,the brain cognitive ability of neonates gradually improves.11-20 days after birth is an important period of auditory brain cognitive development.The cognitive function of the newborn brain has been dominated by the left side of the brain and gender differences.Female newborns show relatively mature cognitive processing abilities compared with males.3.Study on auditory and cognitive development of neonates with different brain maturityObjective:To explore the effects of preterm birth on auditory and cerebral cognitive function of neonates.Methods:Preterm infants(gestational age 28-36+6 weeks)(n=35)and healthy full-term neonates(n=35)were randomly selected in the neonatal department of our hospital.All neonates were diagnosed by neonatologists and had no brain injury during perinatal period.Both ears passed hearing screening,and NBNA scores were≥38.ERP test was performed within 1-7 days of corrected age in the premature infants group and within 1-7 days in the term infants group.The classical Oddball paradigm was used to control the stimulated sound at 50-60 dB SPL.The ERP records and data analysis were the same as before.ERP indexes of preterm and term infants at the same age after birth were compared.Results:(1)The average waveforms of ERP showed that the amplitude of N2 wave in premature infants was low,flat and short,and there was no significant difference between the deviation stimulation and standard stimulation,while P2 wave and N2 wave in full-term infants were significantly different under the two kinds of stimulation.(2)Comparison of P2 and N2 wave areas between premature infants(corrected gestational age)and full-term infants in the first week,Fz and Cz leads,and P2 and N2 wave areas in premature infants were smaller than those in full-term infants(P<0.05).Conclusion:Preterm infants(corrected for gestational age)lag behind full-term infants in perception,sound recognition and attention in the first week,and preterm birth is a major factor affecting cognitive development.Part Ⅱ Study on the cerebral cognitive characteristics and prediction indexes of neurodevelopment in high-risk neonates with hypoxic ischemic encephalopathy(HIE)HIE may result in an abnormal outcome of brain function.In this study,rs-EEG technology was used to analyze PSD and ICOH in combination to explore the cerebral cortex function of children with HIE of different degrees,and to seek neurobiological indicators for early judgment of brain function,so as to facilitate effective monitoring and evaluation in clinical treatment.It will lay a foundation for the next stage of neonatal cognitive early intervention and explore new clinical treatment.It is elaborated in the following two parts:1.Study on the characteristics of brain cognitive function in neonates with different degrees of hypoxic ischemic encephalopathy(HIE)Objective:To investigate the functional characteristics of cerebral cortex in the early stage of hypoxic ischemic encephalopathy(HIE).Methods:Children with HIE admitted to the neonatology department of our hospital were randomly selected.The diagnose of HIE was based on the diagnostic criteria formulated by neonatology Group of Chinese Medical Association in 2005,and they were divided into mild HIE group(n=20)and moderate HIE group(n=15)according to severity(the severe group was not included in this study due to insufficient sample size).Children admitted at the same time without brain injury were selected as the control group(n=30).Rs-EEG was collected in the three groups at 72-96 hours postnatal,and the neonatal 21-lead EEG cap was located by the international 10-20 electrode marker system.The rs-EEG data were analyzed by MATLAB R2014b data processing and analysis software and EEGLAB toolkit.Power spectral density(PSD)and functional linkage analysis(ICOH)were compared among the three groups.Results:(1)PSD study showed that the frequency bands of θ,α and β in FP1,FP2,C3,C4,Fz,Cz,Pz,F3 and P4 in moderate HIE group were significantly decreased compared with mild HIE and control group(P<0.05),and the average PSD of whole brain was significantly decreased(P<0.05).Only the θ band of P4 and a band of Cz in mild HIE group were lower than those in the control group(P<0.05),and the average PSD was not significantly different from that in the control group(P>0.05).(2)ICOH study showed that,compared with the control group,the functional connection intensity of the δ band was significantly decreased in the moderate HIE group,while the functional connection intensity of the δ and α1 band was decreased only in the mild HIE group.Compared with the mild HIE group,functional connection intensity in δ,θ,α1 and α2 bands was decreased in the moderate HIE group.Conclusion:PSD and ICOH can quantitatively analyze the cerebral functional status of HIE neonates,and children with moderate HIE have obvious cortical function lag in the early stage.2.Exploration of early prediction of brain cognitive development in high-risk infantsObjective:To investigate the predictive effects of EEG,ERP and GMs quality assessment on neurodevelopmental status of HIE and other high-risk infants at 1 year old.Methods:71 high-risk neonates admitted to hospital during the study were randomly selected.All patients were diagnosed by neonatologists,and both ears passed hearing screening.Children without brain injury admitted to the department at the same time were selected as the control group.EEG and ERP were detected at 4 weeks of corrected gestational age in high-risk group.At the same time,the quality of GMs was evaluated twice at 4 weeks and 12 weeks of corrected gestational age after birth,and the neurodevelopment was evaluated by Gesell Development Scale at 1 year of corrected age.The EEG and ERP of the control group were measured simultaneously.The values of EEG,GMs quality assessment,EEG+ERP and EEG+ERP+GMs for predicting neurodevelopmental outcome of high-risk neonates were calculated using Gesell evaluation and clinical diagnosis results as neurodevelopmental outcome at 1 year old.Results:(1)Results of Gesell score and clinical diagnosis at 1 year in high-risk infants group:3 cases(4.23%)of cerebral palsy,14 cases(19.72%)of psychomotor retardation,54 cases(76.05%)of normal.(2)EEG,GMs quality assessment,EEG+ERP,EEG+ERP+GMs to predict the neurodevelopmental outcome of high-risk infants at 1 year old:Sensitivity was 76.47%,82.35%,85.71%,90.00%;specificity was 87.04%,83.33%,91.23%,95.08%;positive predictive value was 65.00%,60.87%,70.59%,75.00%;negative predictive values were 92.16%,93.75%,96.30%and 98.31%,respectively.(3)Coefficient consistency test was performed with Gesell score and clinical diagnosis results of cerebral palsy at 1 year old,and Kappa values were 0.599,0.586,0.712 and 0.785,respectively.Conclusion:The combination of EEG,ERP and GMs quality assessment has higher predictive value for the outcome of brain functional development of high-risk neonates at 1 year of age.Part Ⅲ The intervention effect of early auditory stimulation on cerebral function of neonatal asphyxiaBrain plasticity occurs in immature brain and is a compensation mechanism for brain injury.Neonatal brain has strong plasticity.Environment is a key factor affecting plasticity,and brain development is a combination of biological factors and early experience.Early auditory development,26-28 weeks gestation fetus can perceive sound.In this study,EEG quantitative analysis was used to explore the effect of maternal sound and Mozart music auditory stimulation on the early repair of brain function in neonates with asphyxia.1.The early intervention effect of maternal voice stimulation on brain function of neonates with severe asphyxiaObjective:To investigate the early intervention effect of maternal voice collection on brain function of neonates with severe asphyxia.Methods:Neonates with severe asphyxia admitted to NICU of our hospital were randomly selected and divided into severe asphyxia maternal voice intervention(SM)group(n=23)and severe asphyxia control(SC)group(n=19)according to whether they were given maternal voice intervention or not.At the same time,full-term neonates without brain injury in hospital were randomly selected into the normal control group(NC)(n=30).The inclusion criteria and clinical diagnosis and treatment were carried out according to the diagnosis and treatment standards.In the SM group,neonatal maternal voice intervention was initiated 3 days after birth for 10 days.EEG data were collected twice on postnatal days 2-3 and 12-13 in all three groups.All patients were followed up with Gesell scale at 1 year old.Clinical indicators such as heart rate,respiratory rate and percutaneous oxygen saturation(SPO2)were collected during each maternal voice intervention.Results:(1)PSD analysis in δ and θ bands showed that the initial measurement of neonates in SM group and SC group was significantly lower than that in NC group(P<0.05).PSD in SM group was significantly increased after maternal voice therapy compared with SC group(P<0.05).There were differences in PSD of the three groups:SC was significantly lower than NC group(P<0.05),but there was no difference between SC and NC groups.(2)Changes of maternal voice on vital signs:during maternal voice intervention,P and R in SM group were decreased and SPO2 elevated(P<0.05).(3)The instantaneous change of the heart rate when the mother’s voice was played.The heart rates of 18 newborns began to increase about 2 seconds after hearing the mother’s voice,peaked at about 16 seconds,and then gradually decreased to lower than the heart rate before playing the voice.(4)Gesell results at 1 year old showed that no significant difference between SM and NC in the five subscales(P>0.05).But there were obvious differences between SC group and NC group in gross motor behavior,fine motor behavior,adaptive behavior and language behavior(P<0.05).There were significant differences between SM group and SC group in gross motor behavior,adaptive behavior and average DQ(P<0.05).Conclusion:Maternal voice stimulation can stabilize vital signs and improve brain function of neonates with severe asphyxia.2.The early intervention effect of Mozart music on cerebral cognitive function of neonatal asphyxiaObjective:To investigate the effect of Mozart music on cerebral function of asphyxia neonates by rs-EEGMethods:Neonatal asphyxia hospitalized in our hospital were randomly selected and divided into mild asphyxia music intervention(MM)group(n=26),severe asphyxia music intervention(SM)group(n=28),mild asphyxia control(MC)group(n=22),severe asphyxia control(SC)group(n=20).Normal term infants without brain injury were randomly selected into the control group(NC)(n=30)after informed consent.The inclusion criteria and clinical diagnosis and treatment were carried out according to the diagnosis and treatment standards.Both MM group and SM group received early intervention with Mozart’s sonata for two pianos in D major(K.448)3 days after birth for 10 days.Rs-EEG data were collected twice on postnatal days 2-3 and 12-13 for all the five groups.Five groups were evaluated by NBNA at 14 days after birth,and clinical indicators such as heart rate,respiratory rate and percutaneous oxygen saturation(SPO2)were observed.Results:(1)Power spectral density(PSD)of rs-EEG in δ and θ bands was significantly increased after music intervention in MM group and SM group(P<0.05),and the improvement was more obvious in MM than in SM group(P<0.05).Compared with NC group,PSD of MM group,SM group,MC group and SC group in the initial test were significantly lower(P<0.05),and PSD of MC,SC and NC group in the retest was not significantly different from that in the initial test(P>0.05).(2)NBNA results:the score in SC group was much lower than in the NC group(P<0.05),and there were no differences among MM,SM,MC and NC groups(P>0.05).(3)The monitored heart rate and respiratory rate of neonates in MM group and SM group were decreased to varying degrees before and after music intervention(P<0.05),and the changes in MM group were more significant(P<0.05),but there was no statistical significance in the changes of SPO2 between the two groups(P>0.05).Conclusion:Early intervention of Mozart music can improve the brain function of neonates with asphyxia,and the effect of music intervention in mild asphyxia group is better than that in severe asphyxia group.Music can stabilize vital signs,so Mozart music intervention can be used as one of the non-invasive strategies for the treatment of neonatal brain function,which is worth promoting and applying.