Neurologic Consequences of Neonatal Necrotizing Enterocolitis.

Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease of the premature infant with high mortality and morbidity. Children who survive NEC have been shown to demonstrate neurodevelopmental delay, with significantly worse outcomes than from prematurity alone. The pathways leading to NEC-associated neurological impairments remain unclear, limiting the development of preventative and protective strategies. This review aims to summarize the existing clinical and experimental studies related to NEC-associated brain injury. We describe the current epidemiology of NEC, reported long-term neurodevelopmental outcomes among survivors, and proposed pathogenesis of brain injury in NEC. Highlighted are the potential connections between hypoxia-ischemia, nutrition, infection, gut inflammation, and the developing brain in NEC.

Effects of Early and Late Bilingualism on Resting-State Functional Connectivity.

Of current interest is how variations in early language experience shape patterns of functional connectivity in the human brain. In the present study, we compared simultaneous (two languages from birth) and sequential (second language learned after age 5 years) bilinguals using a seed-based resting-state MRI approach. We focused on the inferior frontal gyrus (IFG) as our ROI, as recent studies have demonstrated both neurofunctional and neurostructural changes related to age of second language acquisition in bilinguals in this cortical area. Stronger functional connectivity was observed for simultaneous bilinguals between the left and right IFG, as well as between the inferior frontal gyrus and brain areas involved in language control, including the dorsolateral prefrontal cortex, inferior parietal lobule, and cerebellum. Functional connectivity between the left IFG and the right IFG and right inferior parietal lobule was also significantly correlated with age of acquisition for sequential bilinguals; the earlier the second language was acquired, the stronger was the functional connectivity. In addition, greater functional connectivity between homologous regions of the inferior frontal gyrus was associated with reduced neural activation in the left IFG during speech production. The increased connectivity at rest and reduced neural activation during task performance suggests enhanced neural efficiency in this important brain area involved in both speech production and domain-general cognitive processing. Together, our findings highlight how the brain's intrinsic functional patterns are influenced by the developmental timeline in which second language acquisition occurs. SIGNIFICANCE STATEMENT: Of current interest is how early life experience leaves its footprint on brain structure and function. In this regard, bilingualism provides an optimal way to determine the effects of the timing of language learning because a second language can be learned from birth or later in life. We used resting-state fMRI to look at simultaneous and sequential bilinguals who differed only in age of acquisition, and found stronger connectivity between language and cognitive control regions in bilinguals who learned their two languages simultaneously, a pattern that was associated with more efficient brain activation during speech. Our findings highlight how functional connections in the brain differ depending upon when learning takes place.

Intrinsic Functional Connectivity in the Adult Brain and Success in Second-Language Learning.

There is considerable variability in an individual's ability to acquire a second language (L2) during adulthood. Using resting-state fMRI data acquired before training in English speakers who underwent a 12 week intensive French immersion training course, we investigated whether individual differences in intrinsic resting-state functional connectivity relate to a person's ability to acquire an L2. We focused on two key aspects of language processing--lexical retrieval in spontaneous speech and reading speed--and computed whole-brain functional connectivity from two regions of interest in the language network, namely the left anterior insula/frontal operculum (AI/FO) and the visual word form area (VWFA). Connectivity between the left AI/FO and left posterior superior temporal gyrus (STG) and between the left AI/FO and dorsal anterior cingulate cortex correlated positively with improvement in L2 lexical retrieval in spontaneous speech. Connectivity between the VWFA and left mid-STG correlated positively with improvement in L2 reading speed. These findings are consistent with the different language functions subserved by subcomponents of the language network and suggest that the human capacity to learn an L2 can be predicted by an individual's intrinsic functional connectivity within the language network. Significance statement: There is considerable variability in second-language learning abilities during adulthood. We investigated whether individual differences in intrinsic functional connectivity in the adult brain relate to success in second-language learning, using resting-state functional magnetic resonance imaging in English speakers who underwent a 12 week intensive French immersion training course. We found that pretraining functional connectivity within two different language subnetworks correlated strongly with learning outcome in two different language skills: lexical retrieval in spontaneous speech and reading speed. Our results suggest that the human capacity to learn a second language can be predicted by an individual's intrinsic functional connectivity within the language network.

Neural activation in speech production and reading aloud in native and non-native languages.

We used fMRI to investigate neural activation in reading aloud in bilinguals differing in age of acquisition. Three groups were compared: French-English bilinguals who acquired two languages from birth (simultaneous), French-English bilinguals who learned their L2 after the age of 5 years (sequential), and English-speaking monolinguals. While the bilingual groups contrasted in age of acquisition, they were matched for language proficiency, although sequential bilinguals produced speech with a less native-like accent in their L2 than in their L1. Simultaneous bilinguals activated similar brain regions to an equivalent degree when reading in their two languages. In contrast, sequential bilinguals more strongly activated areas related to speech-motor control and orthographic to phonological mapping, the left inferior frontal gyrus, left premotor cortex, and left fusiform gyrus, when reading aloud in L2 compared to L1. In addition, the activity in these regions showed a significant positive correlation with age of acquisition. The results provide evidence for the engagement of overlapping neural substrates for processing two languages when acquired in native context from birth. However, it appears that the maturation of certain brain regions for both speech production and phonological encoding is limited by a sensitive period for L2 acquisition regardless of language proficiency.

Case Report: Superior Mesenteric Artery Syndrome in an Adolescent With Cannabinoid Hyperemesis.

Background: Superior mesenteric artery syndrome (SMAS) occurs when the third portion of the duodenum is compressed between the superior mesenteric artery (SMA) and the aorta, causing duodenal obstruction. This condition most commonly arises from marked weight loss that reduces the size of the fat pad between these vessels, causing greater acuity of angulation. We present an unusual case of SMAS occurring in an adolescent due to precipitous weight loss resulting from cannabinoid hyperemesis syndrome (CHS). Case Presentation: A 17-year-old adolescent presented emergently with voluminous bilious emesis. She endorsed a history of recent weight loss and a longstanding history of chronic heavy cannabis use associated with recurrent nausea and vomiting. Her chronic symptoms satisfied the Rome IV criteria for cannabinoid hyperemesis syndrome, but her acute vomiting symptoms were more extreme. Evaluation was significant for mild abdominal tenderness and fullness of the epigastrium. Contrast abdominal CT demonstrated moderate gastric and proximal duodenal distention with tapering of the lumen between the SMA and the aorta, consistent with SMAS. Conclusions: To our knowledge, this is the first reported case of SMAS occurring as the result of CHS. Clinicians should be aware of this possible juxtaposition, when a patient with a history of chronic excessive cannabis use, stereotypical vomiting resembling cyclic vomiting syndrome, and considerable rapid weight loss presents with a sudden exacerbation of symptoms, even when a normal BMI is maintained.

A Case of Syphilitic Hepatitis in an Adolescent.

The incidence of syphilis is rising among adolescents necessitating improved provider awareness and screening practices. We present a case of an adolescent with acute hepatitis ultimately diagnosed with secondary syphilitic hepatitis. Clinical presentation, laboratory abnormalities, and histologic features of syphilitic hepatitis are nonspecific, with diagnosis relying on clinical suspicion and targeted testing. This case highlights the importance of screening for syphilis in sexually active adolescents with acute hepatitis. The rising incidence of syphilis among adolescents, and the variety of clinical manifestations including those commonly seen by pediatric gastroenterologists, makes elevated clinical suspicion essential to prompt diagnosis and treatment. With improved provider awareness across general pediatric and subspecialty providers, the transmission of syphilis among adolescent patients can be reduced.

Guardians at the Gate: Early Adversity, Neurocognitive Development, and the Role of the Pediatrician in the Era of COVID-19.

Adverse childhood experiences (ACEs) profoundly impact neurocognitive development. Specifically, when these events occur during critical periods of brain plasticity, a time of significant synaptogenesis, neural pruning, and myelination, typical neurodevelopment can become derailed. Adverse childhood experiences promote morphological changes in neuronal microcircuitry which may lead to diminished cognitive flexibility, inattention, increased impulsivity, decreased school readiness, and disruptive behaviors. In this regard, the current COVID-19 pandemic represents an especially complex adverse experience that disturbs a child's social milieu and support network, likely interfering with brain maturation and executive function. Here, we take a neurodevelopmental approach to argue for the critical role that pediatricians must fulfill in mitigating the potentially detrimental consequences of COVID-19. We call for ACE screening and anticipatory guidance in the primary care setting, and the use of validated interventions and skills to bolster resilience, when ACEs are identified. We present a clinical workflow for the physician to proactively assess, identify, stratify, and address the severity of ACEs worsened by COVID-19. We discuss home-based activities and resources for children and adolescents to promote stress reduction, connectiveness, and self-awareness and create a more positive environment to maximize neurodevelopmental potential in the face of the ongoing pandemic.

Auditory processing disorders in incarcerated youth: A call for early detection and treatment.

BACKGROUND: Numerous reports have linked language impairment, academic underachievement, and attention disorder to misbehavior in adolescence. Recent studies have found an association between deficits in hearing and auditory processing and involvement in the juvenile justice system. In fact, the existence of an auditory processing disorder (APD) is a risk factor for adolescent delinquency even in the presence of normal hearing. The nexus between APD, low academic achievement and offending behavior in teens has prompted recommendation for early screening of school children for abnormalities in auditory processing. Using a variety of diagnostic tools, investigators have found an increase in the frequency of APD in cohorts of confined youthful offenders. The present investigation evaluates the prevalence of APD in a group of incarcerated youth residing in a detention center. METHODS: A total of 52 incarcerated adolescents (8 females and 44 males; age range 13-20 (M = 16.0), residing at a juvenile detention center in Pittsburgh, Pennsylvania and determined to have normal auditory acuity were included in the study. All participants were screened for APD using two dichotic listening tests, the Randomized Dichotic Digits Test (RDDT) and the Dichotic Words Test (DWT), evaluative modalities to identify deficits in auditory processing. The prevalence of APD in the study group was compared to previously published normative data for non-offending age-matched youth. RESULTS: On the RDDT, 23.1% of participants demonstrated normal auditory processing, while 77% had abnormal test results. On the DWT, 75% of subjects exhibited normal auditory processing, while the scores were abnormal for 24.9%. When the results of the RDDT and the DWT were combined to establish a pattern for the purpose of interpreting a deficit, 21.1% of the participants produced results that were within normal limits, while 17.3% qualified for a diagnosis of APD, with abnormal results on both tests. Previous studies have estimated the prevalence of auditory processing disorder in the general adolescent population as being between 2% and 7%. CONCLUSIONS: This study found a higher prevalence of auditory processing disorder in a cohort of incarcerated youth compared with age-matched controls. Diagnostic screening protocols that identify at-risk children have been developed, as have effective therapies to improve auditory processing function. Teachers, pediatricians and psychologists should consider APD in children and adolescents with behaviors that may increase their risk for juvenile justice involvement. Studies on optimal timing and strategies for assessing and treating APD in children and adolescents are needed, including youth caught up in the juvenile justice system.

Early bilingualism, language attainment, and brain development.

The brain demonstrates a remarkable capacity to undergo structural and functional change in response to experience throughout the lifespan. Evidence suggests that, in many domains of skill acquisition, the manifestation of this neuroplasticity depends on the age at which learning begins. The fact that most skills are acquired late in childhood or in adulthood has proven to be a limitation in studies aimed at determining the relationship between age of acquisition and brain plasticity. Bilingualism, however, provides an optimal model for discerning differences in how the brain wires when a skill is acquired from birth, when the brain circuitry for language is being constructed, versus later in life, when the pathways subserving the first language are already well developed. This review examines some of the existing knowledge about optimal periods in language development, with particular attention to the attainment of native-like phonology. It focuses on the differences in brain structure and function between simultaneous and sequential bilinguals and the compensatory mechanisms employed when bilingualism is achieved later in life, based on evidence from studies using a variety of neuroimaging modalities, including positron emission tomography (PET), task-based and resting-state functional magnetic resonance imaging (fMRI), and structural MRI. The discussion concludes with the presentation of recent neuroimaging studies that explore the concept of nested optimal periods in language development and the different neural paths to language proficiency taken by simultaneous and sequential bilinguals, with extrapolation to general notions of the relationship between age of acquisition and ultimate skill performance.

The timing of language learning shapes brain structure associated with articulation.

We compared the brain structure of highly proficient simultaneous (two languages from birth) and sequential (second language after age 5) bilinguals, who differed only in their degree of native-like accent, to determine how the brain develops when a skill is acquired from birth versus later in life. For the simultaneous bilinguals, gray matter density was increased in the left putamen, as well as in the left posterior insula, right dorsolateral prefrontal cortex, and left and right occipital cortex. For the sequential bilinguals, gray matter density was increased in the bilateral premotor cortex. Sequential bilinguals with better accents also showed greater gray matter density in the left putamen, and in several additional brain regions important for sensorimotor integration and speech-motor control. Our findings suggest that second language learning results in enhanced brain structure of specific brain areas, which depends on whether two languages are learned simultaneously or sequentially, and on the extent to which native-like proficiency is acquired.