Bruce Bjornson

Neonatal Pain-Related Stress Predicts Cortical Thickness at Age 7 Years in Children Born Very Preterm

Background Altered brain development is evident in children born very preterm (24–32 weeks gestational age), including reduction in gray and white matter volumes, and thinner cortex, from infancy to adolescence compared to term-born peers. However, many questions remain regarding the etiology. Infants born very preterm are exposed to repeated procedural pain-related stress during a period of very rapid brain development. In this vulnerable population, we have previously found that neonatal pain-related stress is associated with atypical brain development from birth to term-equivalent age. Our present aim was to evaluate whether neonatal pain-related stress (adjusted for clinical confounders of prematurity) is associated with altered cortical thickness in very preterm children at school age. Methods 42 right-handed children born very preterm (24–32 weeks gestational age) followed longitudinally from birth underwent 3-D T1 MRI neuroimaging at mean age 7.9 yrs. Children with severe brain injury and major motor/sensory/cognitive impairment were excluded. Regional cortical thickness was calculated using custom developed software utilizing FreeSurfer segmentation data. The association between neonatal pain-related stress (defined as the number of skin-breaking procedures) accounting for clinical confounders (gestational age, illness severity, infection, mechanical ventilation, surgeries, and morphine exposure), was examined in relation to cortical thickness using constrained principal component analysis followed by generalized linear modeling. Results After correcting for multiple comparisons and adjusting for neonatal clinical factors, greater neonatal pain-related stress was associated with significantly thinner cortex in 21/66 cerebral regions (p-values ranged from 0.00001 to 0.014), predominately in the frontal and parietal lobes. Conclusions In very preterm children without major sensory, motor or cognitive impairments, neonatal pain-related stress appears to be associated with thinner cortex in multiple regions at school age, independent of other neonatal risk factors.

Dichotic Pitch: A new stimulus distinguishes normal and dyslexic auditory function

TWO patterns of appropriately filtered acoustic white noise can be binaurally fused by the human auditory system to extract pitch and location information that is not available to either ear alone. This phenomenon is called dichotic pitch. Here we present a new method for generating more effective and useful dichotic pitch stimuli. These novel stimuli allow the psychophysical assessment of dichotic pitch detection thresholds. We show that dichotic pitch detection is significantly impaired in individuals with developmental dyslexia, as compared to average readers. These results suggest a low-level auditory deficit associated with dyslexia and also demonstrate the potential value of our new dichotic pitch stimuli for assessment of auditory processing.

Psychophysical Indexes of Temporal Processing Abnormalities in Children With Developmental Dyslexia

Children with dyslexia and children progressing normally in reading performed several perceptual tasks to determine (a) the psychophysical measures that best differentiate children with dyslexia from children with average reading abilities; (b) the extent of temporal processing deficits in a single, well-defined group of children with dyslexia; and (c) the co-occurrence of visual and auditory temporal processing deficits in children with dyslexia. 4 of our 12 psychophysical tasks indicated differences in temporal processing ability between children with dyslexia and children with good reading skills. These included 2 auditory tasks (dichotic pitch perception and FM tone discrimination) and 2 visual tasks (global motion perception and contrast sensitivity). The battery of 12 tasks successfully classified 80% of the children into their respective reading-level groups. Within the group of children with dyslexia who had temporal processing deficits, most were affected in either audition or vision; few children were affected in both modalities. The observed deficits suggest that impaired temporal processing in dyslexia is most evident on tasks that require the ability to synthesize local, temporally modulated inputs into a global percept and the ability to extract the resultant global percept from a noisy environment.

Cerebrovascular Reactivity Impairment after Sport-Induced Concussion

PURPOSE This study evaluated cerebrovascular reactivity (CVR) after a sport-induced concussion, also called mild traumatic brain injury (mTBI), by monitoring middle cerebral artery blood velocity (vMCA) with transcranial Doppler ultrasonography and simultaneous end-tidal carbon dioxide (PETCO(2)) measurements. METHODS Thirty-one athletes (16-25 yr old) participated in this study. The participants were divided into two groups-healthy (n = 21) and mTBI (n = 10). Participants in the mTBI group suffered an mTBI within the last 7 d (x- = 4.5 ± 1.1 d). Outcome measures included vMCA and PETCO(2) in response to breath holding (5 × 20 s, 40-s rest) and hyperventilation (5 × 20 s, 40-s rest). RESULTS Resting vMCA values between groups were not significantly different. Percentage change of vMCA was significantly different after the recovery period of the second hyperventilation (P = 0.034). mTBI subjects failed to return to resting levels after each breath hold. PETCO(2) changes mirrored the vMCA changes. CONCLUSIONS These data suggest that normal CVR responses may be disrupted in the days immediately after occurrence of mTBI. Transcranial Doppler ultrasonography combined with expired gas measurements provides a useful method for assessing CVR impairment after mTBI. Further research, including serial monitoring after mTBI and analysis of CVR response to exercise, is warranted before any firm conclusions can be drawn.

Arteriopathy Diagnosis in Childhood Arterial Ischemic Stroke Results of the Vascular Effects of Infection in Pediatric Stroke Study

Background and Purpose Although arteriopathies are the most common cause of childhood arterial ischemic stroke (AIS), and the strongest predictor of recurrent stroke, they are difficult to diagnose. We studied the role of clinical data and follow-up imaging in diagnosing cerebral and cervical arteriopathy in children with AIS.Background and Purpose— Although arteriopathies are the most common cause of childhood arterial ischemic stroke, and the strongest predictor of recurrent stroke, they are difficult to diagnose. We studied the role of clinical data and follow-up imaging in diagnosing cerebral and cervical arteriopathy in children with arterial ischemic stroke. Methods— Vascular effects of infection in pediatric stroke, an international prospective study, enrolled 355 cases of arterial ischemic stroke (age, 29 days to 18 years) at 39 centers. A neuroradiologist and stroke neurologist independently reviewed vascular imaging of the brain (mandatory for inclusion) and neck to establish a diagnosis of arteriopathy (definite, possible, or absent) in 3 steps: (1) baseline imaging alone; (2) plus clinical data; (3) plus follow-up imaging. A 4-person committee, including a second neuroradiologist and stroke neurologist, adjudicated disagreements. Using the final diagnosis as the gold standard, we calculated the sensitivity and specificity of each step. Results— Cases were aged median 7.6 years (interquartile range, 2.8–14 years); 56% boys. The majority (52%) was previously healthy; 41% had follow-up vascular imaging. Only 56 (16%) required adjudication. The gold standard diagnosis was definite arteriopathy in 127 (36%), possible in 34 (9.6%), and absent in 194 (55%). Sensitivity was 79% at step 1, 90% at step 2, and 94% at step 3; specificity was high throughout (99%, 100%, and 100%), as was agreement between reviewers (&kgr;=0.77, 0.81, and 0.78). Conclusions— Clinical data and follow-up imaging help, yet uncertainty in the diagnosis of childhood arteriopathy remains. This presents a challenge to better understanding the mechanisms underlying these arteriopathies and designing strategies for prevention of childhood arterial ischemic stroke.

Risk of Recurrent Arterial Ischemic Stroke in Childhood A Prospective International Study

Background and Purpose— Published cohorts of children with arterial ischemic stroke (AIS) in the 1990s to early 2000s reported 5-year cumulative recurrence rates approaching 20%. Since then, utilization of antithrombotic agents for secondary stroke prevention in children has increased. We sought to determine rates and predictors of recurrent stroke in the current era. Methods— The Vascular Effects of Infection in Pediatric Stroke (VIPS) study enrolled 355 children with AIS at 37 international centers from 2009 to 2014 and followed them prospectively for recurrent stroke. Index and recurrent strokes underwent central review and confirmation, as well as central classification of causes of stroke, including arteriopathies. Other predictors were measured via parental interview or chart review. Results— Of the 355 children, 354 survived their acute index stroke, and 308 (87%) were treated with an antithrombotic medication. During a median follow-up of 2.0 years (interquartile range, 1.0–3.0), 40 children had a recurrent AIS, and none had a hemorrhagic stroke. The cumulative stroke recurrence rate was 6.8% (95% confidence interval, 4.6%–10%) at 1 month and 12% (8.5%–15%) at 1 year. The sole predictor of recurrence was the presence of an arteriopathy, which increased the risk of recurrence 5-fold when compared with an idiopathic AIS (hazard ratio, 5.0; 95% confidence interval, 1.8–14). The 1-year recurrence rate was 32% (95% confidence interval, 18%–51%) for moyamoya, 25% (12%–48%) for transient cerebral arteriopathy, and 19% (8.5%–40%) for arterial dissection. Conclusions— Children with AIS, particularly those with arteriopathy, remain at high risk for recurrent AIS despite increased utilization of antithrombotic agents. Therapies directed at the arteriopathies themselves are needed.

Sub-patterns of language network reorganization in pediatric localization related epilepsy: A multisite study

To study the neural networks reorganization in pediatric epilepsy, a consortium of imaging centers was established to collect functional imaging data. Common paradigms and similar acquisition parameters were used. We studied 122 children (64 control and 58 LRE patients) across five sites using EPI BOLD fMRI and an auditory description decision task. After normalization to the MNI atlas, activation maps generated by FSL were separated into three sub‐groups using a distance method in the principal component analysis (PCA)‐based decisional space. Three activation patterns were identified: (1) the typical distributed network expected for task in left inferior frontal gyrus (Brocas) and along left superior temporal gyrus (Wernickes) (60 controls, 35 patients); (2) a variant left dominant pattern with greater activation in IFG, mesial left frontal lobe, and right cerebellum (three controls, 15 patients); and (3) activation in the right counterparts of the first pattern in Brocas area (one control, eight patients). Patients were over represented in Groups 2 and 3 (P < 0.0004). There were no scanner (P = 0.4) or site effects (P = 0.6). Our data‐driven method for fMRI activation pattern separation is independent of a priori notions and bias inherent in region of interest and visual analyses. In addition to the anticipated atypical right dominant activation pattern, a sub‐pattern was identified that involved intensity and extent differences of activation within the distributed left hemisphere language processing network. These findings suggest a different, perhaps less efficient, cognitive strategy for LRE group to perform the task. Hum Brain Mapp, 2011.

Neonatal Pain and Infection Relate to Smaller Cerebellum in Very Preterm Children at School Age

OBJECTIVE To examine whether specific neonatal factors differentially influence cerebellar subregional volumes and to investigate relationships between subregional volumes and outcomes in very preterm children at 7 years of age. STUDY DESIGN Fifty-six children born very preterm (24-32 weeks gestational age) followed longitudinally from birth underwent 3-dimensional T(1)-weighted neuroimaging at median age 7.6 years. Children with severe brain injury were excluded. Cerebellar subregions were automatically segmented using the multiple automatically generated templates algorithm. The relation between cerebellum subregional volumes (adjusted for total brain volume and sex) and neonatal clinical factors were examined using constrained principal component analysis. Cognitive and visual-motor integration functions in relation to cerebellar volumes were also investigated. RESULTS Higher neonatal procedural pain and infection, as well as other clinical factors, were differentially associated with reduced cerebellar volumes in specific subregions. After adjusting for clinical risk factors, neonatal procedural pain was distinctively associated with smaller volumes bilaterally in the posterior VIIIA and VIIIB lobules. Specific smaller cerebellar subregional volumes were related to poorer cognition and motor/visual integration. CONCLUSIONS In very preterm children, exposure to painful procedures, as well as additional neonatal risk factors such as infection, were associated with reduced cerebellar volumes in specific subregions and poorer outcomes at school age.

Combined functional MRI and diffusion tensor imaging analysis of visual motion pathways.

Background: Motion perception may be preserved after damage to striate cortex (primary visual cortex, area V1). Awareness and normal discrimination of fast-moving stimuli have been observed even in the complete absence of V1. These facts suggest that motion-sensitive cortex (the V5/MT complex or V5/MT+) may be activated by direct thalamic or collicular inputs that bypass V1. Such projections have been identified previously in monkeys but have not been shown in humans using neuroimaging techniques. Methods: We used diffusion tensor imaging (DTI) tractography to visualize white matter fiber tracts connecting with V5/MT+ in 10 healthy volunteers. V5/MT+ was localized for each subject using functional MRI (fMRI). Functional activity maps were overlaid on high-resolution anatomical images and registered with the diffusion-weighted images to define V5/MT+ as the region of interest (ROI) for DTI tractography analysis. Fibers connecting to V1 were excluded from the analysis. Results: Using conservative tractography parameters, we found connections between the V5/MT+ region and the posterior thalamus and/or superior colliculus in 4 of 10 subjects. Conclusions: Connections between the V5/MT+ region and the posterior thalamus and/or superior colliculus may explain visual motion awareness in the absence of a functioning V1.

The role of cortical area V5/MT+ in speed-tuned directional anisotropies in global motion perception

Several different directional anisotropies have been found in global motion perception. The purpose of this study was to examine the role of the motion sensitive cortical area V5/MT+ in directional anisotropies for translational flow fields. Experiments 1 and 2 tested direction discrimination and detection of moving random dot patterns. When the speed of motion was 8 deg/s, lower coherence thresholds were found for centripetal relative to centrifugal hemifield motion. When the speed of motion was 1 deg/s, coherence thresholds were similar in all directions. Experiment 3 used fMRI to measure the BOLD response to different directions of motion at speeds of 1 and 8 deg/s. Greater activity was found in V5/MT+ for centripetal motion than for centrifugal motion at both speeds. These results suggest that V5/MT+ does play a role in directional motion anisotropies. This role is discussed with respect to visually-guided reaching and locomotion.