Perinatal care advances emerging over the past twenty years have helped to diminish the mortality and severe neurological morbidity of extremely and very preterm neonates (e.g., cystic Periventricular Leukomalacia [c-PVL] and Germinal Matrix Hemorrhage - Intraventricular Hemorrhage [GMH-IVH grade 3-4/4]; 22 to < 32 weeks of gestational age, GA). However, motor and/or cognitive disabilities associated with mild-to-moderate white and gray matter injury are frequently present in this population (e.g., non-cystic Periventricular Leukomalacia [non-cystic PVL], neuronal-axonal injury and GMH-IVH grade 1-2/4). Brain research studies using magnetic resonance imaging (MRI) report that 50% to 80% of extremely and very preterm neonates have diffuse white matter abnormalities (WMA) which correspond to only the minimum grade of severity. Nevertheless, mild-to-moderate diffuse WMA has also been associated with significant affectations of motor and cognitive activities. Due to increased neonatal survival and the intrinsic characteristics of diffuse WMA, there is a growing need to study the brain of the premature infant using non-invasive neuroimaging techniques sensitive to microscopic and/or diffuse lesions. This emerging need has led the scientific community to try to bridge the gap between concepts or ideas from different methodologies and approaches; for instance, neuropathology, neuroimaging and clinical findings. This is evident from the combination of intense pre-clinical and clinicopathologic research along with neonatal neurology and quantitative neuroimaging research. In the following review, we explore literature relating the most frequently observed neuropathological patterns with the recent neuroimaging findings in preterm newborns and infants with perinatal brain injury. Specifically, we focus our discussions on the use of neuroimaging to aid diagnosis, measure morphometric brain damage, and track long-term neurodevelopmental outcomes.

The maturation of electroencephalogram (EEG) effective connectivity in healthy infants during the first year of life is described. Participants: A cross-sectional sample of 125 healthy at-term infants, from 0 to 12 months of age, underwent EEG in a state of quiet sleep. The EEG primary currents at the source were described with the sLoreta method. An unmixing algorithm was applied to reduce the leakage, and the isolated effective coherence, a direct and directed measurement of information flow, was calculated. Initially, the highest indices of connectivity are at the subcortical nuclei, continuing to the parietal lobe, predominantly the right hemisphere, then expanding to temporal, occipital, and finally the frontal areas, which is consistent with the myelination process. Age-related connectivity changes were mostly long-range and bilateral. Connections increased with age, mainly in the right hemisphere, while they mainly decreased in the left hemisphere. Increased connectivity from 20 to 30 Hz, mostly at the right hemisphere. These findings were consistent with right hemisphere predominance during the first three years of life. Theta and alpha connections showed the greatest changes with age. Strong connectivity was found between the parietal, temporal, and occipital regions to the frontal lobes, responsible for executive functions and consistent with behavioral development during the first year. The thalamus exchanges information bidirectionally with all cortical regions and frequency bands. The maturation of EEG connectivity during the first year in healthy infants is very consistent with synaptogenesis, reductions in synaptogenesis, myelination, and functional and behavioral development.

Prenatal and perinatal risk factors for perinatal brain damage frequently produce brain injuries in preterm and term infants. The early diagnosis and treatment of these infants, in the period of higher brain plasticity, may prevent the neurological and cognitive sequels that accompany these lesions. The Neurodevelopmental Research Unit at the Institute of Neurobiology of the National Autonomous University of Mexico has taken this endeavor. A multidisciplinary approach is followed. Pediatric, neurologic and rehabilitation clinical studies, MRI, EEG, visual and auditory evoked responses, and Bayley II evaluations are carried out initially. Infants are followed up to 8 years, with periodic appointments for evaluation and treatment. Katona's neurohabilitation method is used for initial diagnosis and treatment. Selective visual and auditory attention are explored from 3 months of age. This method was created in the Unit and, if deficiencies are observed, the method also describes the treatment to avoid subsequent alterations of these processes. Deficiencies in the acquisition of language are evaluated from 4 months of age, implementing treatment through instructions to parents on how they should teach their children to speak. This method has also been developed in the Unit and is in its validation process. In the MRI, we pay special attention to subtle and diffuse patterns, due to the high frequency with which they appear in contemporary cohorts at a national and international level. More than 80% of these infants showed abnormal MRI findings that should be taken into consideration. The outcome of children at 8 years old showed that 78%, 76% and 78% of extremely preterm, very preterm and late preterm, respectively, had a normal neurodevelopment. In term infants, only 69% had a normal neurodevelopment; in this group, the majority of infants had very severe brain lesions. Conclusions: It is necessary to evaluate, at an early age, all newborns with prenatal and perinatal risk factors for brain damage. Special attention should be payed to all premature newborns and those newborns who have been discharged from the intensive care unit.

Background: Preterm birth is one of the world’s critical health problems, with an incidence of 5% to 18% of living newborns according to various countries. White matter injuries due to preoligodendrocytes deficits cause hypomyelination in children born preterm. Preterm infants also have multiple neurodevelopmental sequelae due to prenatal and perinatal risk factors for brain damage. The purpose of this work was to explore the effects of the brain risk factors and MRI volumes and abnormalities on the posterior motor and cognitive development at 3 years of age. Methods: A total of 166 preterm infants were examined before 4 months and clinical and MRI evaluations were performed. MRI showed abnormal findings in 89% of the infants. Parents of all infants were invited to receive the Katona neurohabilitation treatment. The parents of 128 infants accepted and received Katona’s neurohabilitation treatment. The remaining 38 infants did not receive treatment for a variety of reasons. At the three-year follow-up, Bayley’s II Mental Developmental Index (MDI) and the Psychomotor Developmental Index (PDI) were compared between treated and untreated subjects. Results: The treated children had higher values of both indices than the untreated. Linear regression showed that the antecedents of placenta disorders and sepsis as well as volumes of the corpus callosum and of the left lateral ventricle significantly predicted both MDI and PDI, while Apgar < 7 and volume of the right lateral ventricle predicted the PDI. Conclusions: (1) The results indicate that preterm infants who received Katona’s neurohabilitation procedure exhibited significantly better outcomes at 3 years of age compared to those who did not receive the treatment. (2) The presence of sepsis and the volumes of the corpus callosum and lateral ventricles at 3–4 months were significant predictors of the outcome at 3 years of age.