Early brain injury in children: development and reorganization of cognitive function

Children who sustain congenital or acquired brain injury typically experience a diffuse insult that impacts many areas of the brain. Yet research has only recently begun to examine the development of these children, who often provide excellent examples of the presence or absence of neural plasticity. Development and recovery after such injuries reflects both restoration and reorganization of cognitive functions. To understand these processes, research should focus on questions and assessment paradigms oriented toward the acquisition (rather than the recovery) of cognitive functions. Outcomes may appear similar across types of insults, even when the sources of difficulties and their neural correlates are different. Comparisons of outcomes involving intellectual functions, memory and learning, reading, and language/discourse in children who sustain congenital injury (spina bifida meningomyelocele) and acquired injury (traumatic brain injury) illustrate these principles and the value of research on diffuse brain injury in children.     

Patterns of developmental and behavioral progress for young brain‐injured children during interdisciplinary intervention

Pediatric hospital rehabilitation teams and community‐based early intervention programs confront the increasing demand to treat infants and preschoolers suffering both acquired and congenital brain injuries. However, few outcome studies are available to provide clear and practical guidance to their efforts. Specialists require more complete knowledge of the problems and the possibilities for these young handicapped children. Needed research can establish norms for progress and recovery, which can be used to evaluate individual gains, to provide prognoses, and to monitor interdisciplinary treatment impact. Our preliminary research traced comparative patterns of developmental and behavioral progress during intervention for infants and preschoolers suffering acquired and congenital brain injuries. In addition, this study documented treatment impact for both brain injury groups. Results demonstrated the existence of very similar overall progress and recovery patterns within both groups. An intensive interdisiplinary treatment approach proved to be responsible for facilitating developmental and behavioral gains beyond levels expected due to maturation. Practical implications of these results for early intervention teams are detailed.     

Memory functioning following traumatic brain injury in children with premorbid learning problems

This study examines the memory functioning of 25 children who sustained a traumatic brain injury (TBI) and who had prior learning problems, 48 children with TBI who did not have prior learning problems, and 23 noninjured controls. The children with TBI and prior learning problems displayed significantly worse memory abilities than both the control participants and the children with TBI and no prior learning problems. They differed significantly from these 2 groups on measures of general memory, verbal memory, sound-symbol learning, and attention. The results suggest that children with premorbid learning problems who sustain TBI have less cognitive reserve and a lower threshold for the expression of cognitive impairments in areas that reflect preexisting learning and language problems, compared to children without premorbid learning problems.     

Memory Functioning Following Traumatic Brain Injury in Children With Premorbid Learning Problems

This study examines the memory functioning of 25 children who sustained a traumatic brain injury (TBI) and who had prior learning problems, 48 children with TBI who did not have prior learning problems, and 23 noninjured controls. The children with TBI and prior learning problems displayed significantly worse memory abilities than both the control participants and the children with TBI and no prior learning problems. They differed significantly from these 2 groups on measures of general memory, verbal memory, sound-symbol learning, and attention. The results suggest that children with premorbid learning problems who sustain TBI have less cognitive reserve and a lower threshold for the expression of cognitive impairments in areas that reflect preexisting learning and language problems, compared to children without premorbid learning problems.     

Preschool children with mild to moderate traumatic brain injury: an exploration of immediate and post-acute morbidity.

This study explored premorbid, neurocognitive, behavioral, and familial factors in preschoolers, ages 3-6, who experienced a mild to moderate traumatic brain injury (TBI). Twenty-nine children with TBI, 33 children with mild to moderate injuries to other body regions, and 34 non-injured children participated in the study. Neuropsychological assessments and behavioral measures were administered at the time of hospitalization and 6 months later. In comparison to the non-injury children, preschool-aged children with TBI had higher rates of premorbid behavior difficulties, lower premorbid cognitive functioning, and poorer development of pre-academic skills. In addition, parents of children with TBI reported greater situational issues and life stressors than parents of children in the non-injured group. Some neurocognitive recovery was evident in the TBI group, but no differences were recognized in behavioral and family measures at the 6-month follow-up. This study emphasizes the relative effects of premorbid characteristics in later practice of preschool children who sustain TBI.     

Magnesium attenuates persistent functional deficits following diffuse traumatic brain injury in rats

Although a number of studies have demonstrated that magnesium improves acute motor and cognitive outcome after traumatic brain injury, others have failed to show positive effects on cognitive outcome and none have examined persistent functional deficits. The present study shows that severe impact-acceleration induced, diffuse traumatic brain injury in rats produced profound motor and cognitive deficits that persisted for at least 4 weeks after trauma. Intravenous administration of magnesium sulfate (250 micromoles/kg) at 30 min after injury significantly improved rotarod (sensorimotor) and open field (stress/anxiety) performance, and led to a faster rate of recovery in the Barnes maze (learning). We conclude that posttraumatic magnesium administration attenuates long-term motor and cognitive deficits after traumatic brain injury, and that this improvement may include some reduction of post-traumatic stress and anxiety.     

Genetic vulnerability following traumatic brain injury: the role of apolipoprotein E.

Apolipoprotein E (APOE) is thought to be responsible for the transportation of lipids within the brain, maintaining structural integrity of the microtubule within the neurone, and assisting with neural transmission. Possession of the APOE epsilon4 allele has also been shown to influence neuropathological findings in patients who die from traumatic brain injury, including the accumulation of amyloid beta protein. Previous clinical studies reporting varying outcome severities of traumatic brain injury, including cognitive and functional recovery, all support the notion that APOE epsilon4 allele possession is associated with an unfavourable outcome. Evidence from experimental and clinical brain injury studies confirms that APOE plays an important role in the response of the brain to injury.     

The lesion methodology: contrasting views from adult and child studies

A traditional approach for examining brain-behavior relations has been the lesion method. This method assumes a direct correspondence between the cognitive process compromised and the site of lesion. Historically, studies with adults have used this framework to map brain functions. In contrast, studies of children with early injury have addressed quite different issues. Developmental animal lesion studies and pediatric neuropsychology studies have focused on the level of plasticity exhibited following early injury. Resilency in behavioral development has suggested change in the underlying neural substrate. A new set of studies has applied converging, MRI-based methods to examine anatomical and functional development in intact brain regions following early injury and compared these data with behavioral outcomes on the same children. The findings reveal an interaction between early injury and normal mechanisms of development, which manifest as atypical behavioral, structural, and functional development.     

Genetic aspects of early childhood scoliosis

Eighty-seven families with early onset scoliosis were evaluated. These were divided into 3 groups: resolving infantile idiopathic scoliosis (15 families), progressive infantile idiopathic scoliosis (21 families), and congenital scoliosis due to vertebral malformations (51 families). The children with congenital scoliosis were subdivided into those who had closed neural arch defects (19 families) and those who did not (32 families). Resolving infantile idiopathic scoliosis was usually associated with plagiocephaly, and both deformations tended to show spontaneous recovery. These children were otherwise normal. Seven (33%) of the children with progressive infantile idiopathic scoliosis were mentally retarded, but only 2 had a congenital malformation. In contrast, 18 (33%) of the children with congenital scoliosis had other malformations, but only 2 were mentally retarded. The recurrence risk for scoliosis was low in each group studied. However, there was an increased risk (4% for sibs) of neural tube defects in the families with congenital scoliosis (with or without neural arch defects). This sib risk was apparent for probands with only a single hemivertebrum in addition to probands with more extensive vertebral defects and would support an etiological relationship between neural tube defects and other vertebral malformations.     

Response inhibition after traumatic brain injury (TBI) in children: impairment and recovery

Children who experience traumatic brain injury (TBI) often show cognitive impairments postinjury, some of which recover over time. We examined the recovery of motor response inhibition immediately following TBI and over 2 years. We assessed the role of injury severity, age at injury, and lesion characteristics on initial impairment and recovery while considering the role of pre-injury psychiatric disorder. Participants were 136 children with TBI aged 5-16 years. Latency of motor response inhibition was measured with the stop-signal task within 1 month of the injury and again at 3, 6, 12, and 24 months. The performance of the TBI participants at each measurement occasion was standardized with 117 children of similar age, but without injury. Residualized latency scores were calculated. Growth curve analyses showed an initial impairment in response inhibition and improvement over the 2 years following injury. Younger TBI patients were initially more impaired although they exhibited greater recovery of response inhibition than did older TBI patients. Longer duration of coma, but not reactivity of pupils or Glasgow Coma Scale score, predicted initial deficit. Lesion characteristics or pre-injury attention deficit hyperactivity disorder did not predict initial impairment or recovery. Replication with longitudinal testing of a comparison group of children sustaining extracranial injury is necessary to confirm our findings.     

Response Inhibition After Traumatic Brain Injury (TBI) in Children: Impairment and Recovery

Children who experience traumatic brain injury (TBI) often show cognitive impairments postinjury, some of which recover over time. We examined the recovery of motor response inhibition immediately following TBI and over 2 years. We assessed the role of injury severity, age at injury, and lesion characteristics on initial impairment and recovery while considering the role of pre-injury psychiatric disorder. Participants were 136 children with TBI aged 5–16 years. Latency of motor response inhibition was measured with the stop-signal task within 1 month of the injury and again at 3, 6, 12, and 24 months. The performance of the TBI participants at each measurement occasion was standardized with 117 children of similar age, but without injury. Residualized latency scores were calculated. Growth curve analyses showed an initial impairment in response inhibition and improvement over the 2 years following injury. Younger TBI patients were initially more impaired although they exhibited greater recovery of response inhibition than did older TBI patients. Longer duration of coma, but not reactivity of pupils or Glasgow Coma Scale score, predicted initial deficit. Lesion characteristics or pre-injury attention deficit hyperactivity disorder did not predict initial impairment or recovery. Replication with longitudinal testing of a comparison group of children sustaining extracranial injury is necessary to confirm our findings.     

New insights from children with early focal brain injury: Lessons to be learned from examining STEM-related skills

The study of cognitive development in children with early brain injury reveals crucial information about the developing brain and its plasticity. However, information on long-term outcomes of these children, especially in domains relevant to science, technology, engineering, and math (STEM) remains limited. In the current review, our goal is to address the existing research on cognitive development of children with pre- or perinatal focal brain lesion (PL) as it relates to children's STEM-related skills and suggest future work that could shed further light on the developmental trajectories of children with PL. We argue that examining STEM-related development in children with PL will have broader implications for our understanding of the nature of the plasticity children with PL exhibit as well as address theoretical questions in the field regarding the foundation skills for STEM, including visuospatial and mathematical skills.     

Genetic aspects of early chiidhood scoliosis

Eighty-seven families with early onset sccoliosis were evaluated. These were divided into 3 groups: resolving infantile idiopathic scoliosis (15 families), progressive infantile idiopathic scoliosis (21 families), and congenital scoliosis due to vertebral malformations (51 families). The children with congenital scoliosis were subdivided into those who had closed neural arch defect (19 families) and those who did not (32 families). Resolving infantile idiopathic scoliosis was usually associated with plagiocephaly, and both deformations tended to show spontaneous recovery. These children were otherwise normal. Seven (33%) of the children with progressive infantile idiopathic scoliosis were mnentally retarded, but only 2 had a congenital malformation. In contrast, 18 (33%) of the children with congential scoliosis had other malformations, but only 2 were mentally retarded. The recurrence risk for scoliosis was low in each group studied. However, there was an incriased risk (4% for sibs) of neural tube defects in the families with congenital scoliosis (with or without neural arch defects). This sib resk was apparent for probands with only a single hemivetebrum in addition to probands with more extensive vertebral defects and would support an etiological relationship between neural tube defects and other vertebral malformations.     

Regression-predicted age norms for the Children's Orientation and Amnesia Test.

The Children's Orientation and Amnesia Test (COAT) was developed to assess posttraumatic amnesia (PTA) and cognitive functioning in children and adolescents who are in the early stages of recovery from traumatic brain injury. The COAT is composed of 16 items designed to assess general orientation, temporal orientation, and memory. The original norms are inadequate for several age groups because they were based on small sample sizes and may have been compromised by ceiling effects. In this study, normative data were collected for children between the ages of 8 and 13 (N=248). Regression-predicted age norms were calculated and presented in tabular form. These results provide important reference data for interpreting COAT scores of children who have sustained traumatic brain injuries.     

Assessment of cognitive function following magnesium therapy in the traumatically injured brain.

Many studies have examined the preclinical efficacy of Mg2+ therapy in models of traumatic brain injury. However, more of these studies have examined sensorimotor and motor performance than cognitive performance following injury. The present paper reviews the use of Mg2+ therapy to facilitate cognitive recovery in several models of cortical injury in the rodent. The first study examined the ability of daily injections of MgCl2 (1 or 2 mmol) to impair acquisition of a reference memory task in the Morris Water Maze. Additional studies examined the ability of MgCl2 to improve cognitive function following bilateral anterior medial cortex ablations, bilateral frontal cortex contusions, and unilateral frontal contusions. The results from these studies indicate that MgCl2 therapy is biologically active and readily crosses the blood-brain barrier because daily injections of MgCl2 impaired learning of a reference memory task in intact rats. Mg2+ therapy for brain injury revealed that administration of post-injury MgCl2 effectively improved recovery of cognitive deficits following injury. These results suggest that Mg2+ therapy is effective in facilitating cognitive recovery of function following brain injury; however, there are task and dose-dependent aspects to this recovery.     

Structural and functional brain development and its relation to cognitive development

Despite significant gains in the fields of pediatric neuroimaging and developmental neurobiology, surprisingly little is known about the developing human brain or the neural bases of cognitive development. This paper addresses MRI studies of structural and functional changes in the developing human brain and their relation to changes in cognitive processes over the first few decades of human life. Based on post-mortem and pediatric neuroimaging studies published to date, the prefrontal cortex appears to be one of the last brain regions to mature. Given the prolonged physiological development and organization of the prefrontal cortex during childhood, tasks believed to involve this region are ideal for investigating the neural bases of cognitive development. A number of normative pediatric fMRI studies examining prefrontal cortical activity in children during memory and attention tasks are reported. These studies, while largely limited to the domain of prefrontal functioning and its development, lend support for continued development of attention and memory both behaviorally and physiologically throughout childhood and adolescence. Specifically, the magnitude of activity observed in these studies was greater and more diffuse in children relative to adults. These findings are consistent with the view that increasing cognitive capacity during childhood may coincide with a gradual loss rather than formation of new synapses and presumably a strengthening of remaining synaptic connections. It is clear that innovative methods like fMRI together with MRI-based morphometry and nonhuman primate studies will transform our current understanding of human brain development and its relation to behavioral development.     

Evaluation of the effects of treatment with sAPPα on functional and histological outcome following controlled cortical impact injury in mice

Treatment with sAPPα, the product of non-amyloidogenic processing of the amyloid precursor protein (APP) has been shown to be protective following diffuse traumatic brain injury (TBI), by improving motor outcome and reducing axonal injury. However the effects of treatment with sAPPα following a focal TBI have yet to be determined. To investigate this, mice were subjected to a controlled cortical impact injury and treated with either sAPPα or its vehicle at 30 min post-injury. Following treatment with sAPPα the mice showed a significant improvement in motor and cognitive function early following injury, as determined on the ledged beam and Barnes Maze, respectively, relating to a more rapid rate of recovery. However the effect of treatment with sAPPα was not as dramatic as that seen previously following a diffuse injury. Nonetheless, these improvements in functional outcome were acompanied by a small but significant improvement in the amount of cortical and hippocampal at 7 days post-injury, and provide further support for the efficacy of sAPPα as a potential neuroprotective agent following TBI.     

脑外伤病人记忆功能的康复特点

脑外伤现已成为危害人们健康的主要疾病之一。脑外伤会引起多种认知功能障碍 ,如注意、记忆和语言等 ,其中记忆障碍较为常见。脑外伤后会有一段时间失去意识 ,同时伴有失定向、意识混乱 ,以及情节记忆受损等症状 ,称为创伤后遗忘 (ｐｏｓｔｔｒａｕ ｍａｔｉｃａｍｎｅｓｉａ ,ＰＴＡ) [1- 3] 。ＰＴＡ可以持续几分钟或几个月不等 ,它对于预测脑外伤后认知功能康复的程度等有重要的参考价值 ,ＰＴＡ的持续时间短 ,程度轻 ,其后认知功能的康复就会较好。对ＰＴＡ最简单的评价是询问病人在外伤后能够记起的第一件事 ,以及病人能够记起的外伤前…     

Cognitive and neural plasticity in old age: A systematic review of evidence from executive functions cognitive training

Cognitive training is a popular intervention aimed at attenuating age-related cognitive decline, however, the effects of this intervention on brain structure and function have not been thoroughly explored. Core executive functions (working memory, inhibition, cognitive flexibility) are dependent upon prefrontal brain regions—one of the most vulnerable areas of age-related decline. They are also implicated in numerous cognitive processes and higher-order functions. Training executive functions should therefore promote cognitive and neural enhancements in old age. This systematic review examined the effects of executive functions training on brain and cognition amongst healthy older adults across 20 studies. Behavioral performance consistently improved on trained cognitive tasks, though mixed findings were reported for untrained tasks. Training-related structural changes were reported, evidenced through increases in grey matter and cortical volume. Functional changes were not consistent, though a general pattern of increased subcortical and decreased frontal and parietal activation emerged across studies, indicating that training may potentially reduce reliance on compensatory neural mechanisms. Training executive functions appears to promote cognitive and neural plasticity in old age, though further research is required to develop a more comprehensive framework which connects and elucidates the mechanisms underlying cognitive training, cognitive transfer, and cognitive aging.     

Effects of day-of-injury alcohol intoxication on neuropsychological outcome in the acute recovery period following traumatic brain injury

Some researchers have found that day-of-injury alcohol intoxication is associated with worse outcome following traumatic brain injury (TBI). The purpose of this study is to examine the effects of day-of-injury intoxication on the acute neuropsychological outcome from TBI. Participants were 36 patients with TBI (18 sober, 18 intoxicated) matched on injury severity characteristics and demographic variables. A larger group of 146 patients (112 sober, 36 intoxicated) with TBI was also selected for analyses; not matched on injury severity or demographic variables. Patients had no history of pre-injury alcoholism and were assessed within 10 days post-injury on 13 cognitive measures. Unexpectedly, patients who were sober at the time of injury performed lower on many of the cognitive measures compared to those who were intoxicated. In contrast to the research literature, these results suggest that individuals who were intoxicated at the time of injury performed similarly, and in some cases, better than those who were sober at the time of injury.