Global motion detection and censoring in high-density diffuse optical tomography.

Motion-induced artifacts can significantly corrupt optical neuroimaging, as in most neuroimaging modalities. For high-density diffuse optical tomography (HD-DOT) with hundreds to thousands of source-detector pair measurements, motion detection methods are underdeveloped relative to both functional magnetic resonance imaging (fMRI) and standard functional near-infrared spectroscopy (fNIRS). This limitation restricts the application of HD-DOT in many challenging imaging situations and subject populations (e.g., bedside monitoring and children). Here, we evaluated a new motion detection method for multi-channel optical imaging systems that leverages spatial patterns across measurement channels. Specifically, we introduced a global variance of temporal derivatives (GVTD) metric as a motion detection index. We showed that GVTD strongly correlates with external measures of motion and has high sensitivity and specificity to instructed motion-with an area under the receiver operator characteristic curve of 0.88, calculated based on five different types of instructed motion. Additionally, we showed that applying GVTD-based motion censoring on both hearing words task and resting state HD-DOT data with natural head motion results in an improved spatial similarity to fMRI mapping. We then compared the GVTD similarity scores with several commonly used motion correction methods described in the fNIRS literature, including correlation-based signal improvement (CBSI), temporal derivative distribution repair (TDDR), wavelet filtering, and targeted principal component analysis (tPCA). We find that GVTD motion censoring on HD-DOT data outperforms other methods and results in spatial maps more similar to those of matched fMRI data.

Lower Urinary Tract Dysfunction and Associated Pons Volume in Patients with Wolfram Syndrome.

PURPOSE: Wolfram syndrome is a neurodegenerative disorder characterized by childhood onset diabetes mellitus, optic nerve atrophy, diabetes insipidus, hearing impairment, and commonly bladder and bowel dysfunction. We hypothesized that there is an association between a smaller pons, which contains the pontine micturition center, and abnormal lower urinary tract function. MATERIALS AND METHODS: Patients with genetically confirmed Wolfram syndrome attended an annual multidisciplinary research clinic. Subjects underwent noninvasive urodynamic testing and brain magnetic resonance imaging, and completed validated patient reported outcome measures. Bowel and bladder diaries were completed before visits. Age and gender corrected linear and logistic mixed effects models were used to correlate pons volume, corrected for whole brain size, to urodynamic and patient reported outcomes. RESULTS: A total of 36 patients attended 142 visits between 2010 and 2016. Mean age was 16.9 years (range 7 to 30) and 64% of patients were female. Functional bladder capacity was decreased in 31% of the patients, normal in 54% and increased in 14%. Of the patients 44% and 54% had abnormal uroflowmetry and post-void residual, respectively, on at least 1 occasion. There was no increase through time in incidence of lower urinary tract dysfunction. Decreased pons volume was associated with increased post-void residual (p = 0.048) and higher PinQ (Pediatric Incontinence Questionnaire) score (p = 0.011), indicating lower quality of life and higher levels of dysfunction. CONCLUSIONS: A significant number of children, adolescents and young adults with Wolfram syndrome have objective evidence of lower urinary tract dysfunction. Decreased pons volume is associated with more abnormal urinary function and lower quality of life in patients with Wolfram syndrome.

Functional anatomy of subthalamic nucleus stimulation in Parkinson disease.

OBJECTIVE: We developed a novel method to map behavioral effects of deep brain stimulation (DBS) across a 3-dimensional brain region and to assign statistical significance after stringent type I error correction. This method was applied to behavioral changes in Parkinson disease (PD) induced by subthalamic nucleus (STN) DBS to determine whether these responses depended on anatomical location of DBS. METHODS: Fifty-one PD participants with STN DBS were evaluated off medication, with DBS off and during unilateral STN DBS with clinically optimized settings. Dependent variables included DBS-induced changes in Unified Parkinson Disease Rating Scale (UPDRS) subscores, kinematic measures of bradykinesia and rigidity, working memory, response inhibition, mood, anxiety, and akathisia. Weighted t tests at each voxel produced p images showing where DBS most significantly affected each dependent variable based on outcomes of participants with nearby DBS. Finally, a permutation test computed the probability that this p image indicated significantly different responses based on stimulation site. RESULTS: Most motor variables improved with DBS anywhere in the STN region, but several motor, cognitive, and affective responses significantly depended on precise location stimulated, with peak p values in superior STN/zona incerta (quantified bradykinesia), dorsal STN (mood, anxiety), and inferior STN/substantia nigra (UPDRS tremor, working memory). INTERPRETATION: Our method identified DBS-induced behavioral changes that depended significantly on DBS site. These results do not support complete functional segregation within STN, because movement improved with DBS throughout, and mood improved with dorsal STN DBS. Rather, findings support functional convergence of motor, cognitive, and limbic information in STN.

Mood response to deep brain stimulation of the subthalamic nucleus in Parkinson's disease.

Deep brain stimulation of the subthalamic nucleus (STN DBS) in Parkinson's disease (PD) improves motor functioning but has variable effects on mood. Little is known about the relationship between electrode contact location and mood response. The authors identified the anatomical location of electrode contacts and measured mood response to stimulation with the Visual Analog Scale in 24 STN DBS PD patients. Participants reported greater positive mood and decreased anxiety and apathy with bilateral and unilateral stimulation. Left DBS improved mood more than right DBS. Right DBS-induced increase in positive mood was related to more medial and dorsal contact locations. These results highlight the functional heterogeneity of the STN.

Plasma Neurofilament Light Chain Levels Are Elevated in Children and Young Adults With Wolfram Syndrome.

Wolfram syndrome is a rare disease caused by pathogenic variants in the WFS1 gene with progressive neurodegeneration. As an easily accessible biomarker of progression of neurodegeneration has not yet been found, accurate tracking of the neurodegenerative process over time requires assessment by costly and time-consuming clinical measures and brain magnetic resonance imaging (MRI). A blood-based measure of neurodegeneration, neurofilament light chain (NfL), is relatively inexpensive and can be repeatedly measured at remote sites, standardized, and measured in individuals with MRI contraindications. To determine whether NfL levels may be of use in disease monitoring and reflect disease activity in Wolfram syndrome, plasma NfL levels were compared between children and young adults with Wolfram syndrome (n = 38) and controls composed of their siblings and parents (n = 35) and related to clinical severity and selected brain region volumes within the Wolfram group. NfL levels were higher in the Wolfram group [median (interquartile range) NfL = 11.3 (7.8-13.9) pg/mL] relative to controls [5.6 (4.5-7.4) pg/mL]. Within the Wolfram group, higher NfL levels related to worse visual acuity, color vision and smell identification, smaller brainstem and thalamic volumes, and faster annual rate of decrease in thalamic volume over time. Our findings suggest that plasma NfL levels can be a powerful tool to non-invasively assess underlying neurodegenerative processes in children, adolescents and young adults with Wolfram syndrome.

Mapping Go-No-Go performance within the subthalamic nucleus region.

The basal ganglia are thought to be important in the selection of wanted and the suppression of unwanted motor patterns according to explicit rules (i.e. response inhibition). The subthalamic nucleus has been hypothesized to play a particularly critical role in this function. Deep brain stimulation of the subthalamic nucleus in individuals with Parkinson's disease has been used to test this hypothesis, but results have been variable. Based on current knowledge of the anatomical organization of the subthalamic nucleus, we propose that the location of the contacts used in deep brain stimulation could explain variability in the effects of deep brain stimulation of the subthalamic nucleus on response inhibition tasks. We hypothesized that stimulation affecting the dorsal subthalamic nucleus (connected to the motor cortex) would be more likely to affect motor symptoms of Parkinson's disease, and stimulation affecting the ventral subthalamic nucleus (connected to higher order cortical regions) would be more likely to affect performance on a response inhibition task. We recruited 10 individuals with Parkinson's disease and bilateral deep brain stimulation of the subthalamic nucleus with one contact in the dorsal and another in the ventral subthalamic region on one side of the brain. Patients were tested with a Go-No-Go task and a motor rating scale in three conditions: stimulation off, unilateral dorsal stimulation and unilateral ventral stimulation. Both dorsal and ventral stimulation improved motor symptoms, but only ventral subthalamic stimulation affected Go-No-Go performance, decreasing hits and increasing false alarms, but not altering reaction times. These results suggest that the ventral subthalamic nucleus is involved in the balance between appropriate selection and inhibition of prepotent responses in cognitive paradigms, but that a wide area of the subthalamic nucleus region is involved in the motor symptoms of Parkinson's disease. This finding has implications for resolving inconsistencies in previous research, highlights the role of the ventral subthalamic nucleus region in response inhibition and suggests an approach for the clinical optimization of deep brain stimulation of the subthalamic nucleus for both motor and cognitive functions.

A developmental fMRI study of reading and repetition reveals changes in phonological and visual mechanisms over age.

In this study of reading development, children (ages 7-10) and adults (ages 18-32) performed overt single-word reading and aural repetition tasks on high-frequency word stimuli during functional magnetic resonance imaging. Most regions showed similar activity across age groups. These widespread regions of similarity indicate that children and adults use largely overlapping mechanisms when processing high-frequency words. Significant task-related differences included greater activity in occipital cortex for the read task, and greater activity in temporal cortex for the repeat task; activity levels in these regions were similar for adults and children. However, age group differences were found in several posterior regions, including a set of regions implicated in adult reading: the left supramarginal gyrus, the left angular gyrus, and bilateral anterior extrastriate cortex. The angular and supramarginal gyrus regions, hypothesized to play a role in phonology, showed decreased activity in adults relative to children for high-frequency words. The extrastriate regions had significant activity for both the visual read task and auditory repeat task in children, but just for the read task in adults, showing significant task and age interactions. These results are consistent with decreasing reliance on phonological processing, and increasing tuning of visual mechanisms, with age.

Sleep disturbances in Wolfram syndrome.

BACKGROUND: Wolfram syndrome is a rare disorder associated with diabetes mellitus, diabetes insipidus, optic nerve atrophy, hearing and vision loss, and neurodegeneration. Sleep complaints are common but have not been studied with objective measures. Our goal was to assess rates of sleep apnea and objective and self-reported measures of sleep quality, and to determine the relationship of sleep pathology to other clinical variables in Wolfram syndrome patients. METHODS: Genetically confirmed Wolfram syndrome patients were evaluated at the 2015 and 2016 Washington University Wolfram Syndrome Research Clinics. Patients wore an actigraphy device and a type III ambulatory sleep study device and completed the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index (PSQI) and/or the Pediatric Sleep Questionnaire (PSQ). PSQI and PSQ questionnaire data were compared to a previously collected group of controls. Patients were characterized clinically with the Wolfram Unified Rating Scale (WURS) and a subset underwent magnetic resonance imaging (MRI) for brain volume measurements. RESULTS: Twenty-one patients were evaluated ranging from age 8.9-29.7 years. Five of 17 (29%) adult patients fit the criteria for obstructive sleep apnea (OSA; apnea-hypopnea index [AHI] ≥ 5) and all 4 of 4 (100%) children aged 12 years or younger fit the criteria for obstructive sleep apnea (AHI's ≥ 1). Higher AHI was related to greater disease severity (higher WURS Physical scores). Higher mixed apnea scores were related to lower brainstem and cerebellar volumes. Patients' scores on the PSQ were higher than those of controls, indicating greater severity of childhood obstructive sleep-related breathing disorders. CONCLUSIONS: Wolfram syndrome patients had a high rate of OSA. Further study would be needed to assess how these symptoms change over time. Addressing sleep disorders in Wolfram syndrome patients would likely improve their overall health and quality of life.

Evidence for altered neurodevelopment and neurodegeneration in Wolfram syndrome using longitudinal morphometry.

Wolfram syndrome is a rare disease caused by mutations in the WFS1 gene leading to symptoms in early to mid-childhood. Brain structural abnormalities are present even in young children, but it is not known when these abnormalities arise. Such information is critical in determining optimal outcome measures for clinical trials and in understanding the aberrant neurobiological processes in Wolfram syndrome. Using voxel-wise and regional longitudinal analyses, we compared brain volumes in Wolfram patients (n = 29; ages 5-25 at baseline; mean follow-up = 3.6 years), to age and sex-equivalent controls (n = 52; ages 6-26 at baseline; mean follow-up = 2.0 years). Between groups, white and gray matter volumes were affected differentially during development. Controls had uniformly increasing volume in white matter, whereas the Wolfram group had stable (optic radiations) or decreasing (brainstem, ventral pons) white matter volumes. In gray matter, controls had stable (thalamus, cerebellar cortex) or decreasing volumes (cortex), whereas the Wolfram group had decreased volume in thalamus and cerebellar cortex. These patterns suggest that there may be early, stalled white matter development in Wolfram syndrome, with additional degenerative processes in both white and gray matter. Ideally, animal models could be used to identify the underlying mechanisms and develop specific interventions.

Neuroimaging evidence of deficient axon myelination in Wolfram syndrome.

Wolfram syndrome is a rare autosomal recessive genetic disease characterized by insulin dependent diabetes and vision, hearing and brain abnormalities which generally emerge in childhood. Mutations in the WFS1 gene predispose cells to endoplasmic reticulum stress-mediated apoptosis and may induce myelin degradation in neuronal cell models. However, in vivo evidence of this phenomenon in humans is lacking. White matter microstructure and regional volumes were measured using magnetic resonance imaging in children and young adults with Wolfram syndrome (n = 21) and healthy and diabetic controls (n = 50). Wolfram patients had lower fractional anisotropy and higher radial diffusivity in major white matter tracts and lower volume in the basilar (ventral) pons, cerebellar white matter and visual cortex. Correlations were found between key brain findings and overall neurological symptoms. This pattern of findings suggests that reduction in myelin is a primary neuropathological feature of Wolfram syndrome. Endoplasmic reticulum stress-related dysfunction in Wolfram syndrome may interact with the development of myelin or promote degeneration of myelin during the progression of the disease. These measures may provide objective indices of Wolfram syndrome pathophysiology that will be useful in unraveling the underlying mechanisms and in testing the impact of treatments on the brain.

Hippocampal Volume in Type 1 Diabetes.

The hippocampus plays an important role in human memory and is known to be vulnerable to extreme hyperglycaemia and hypoglycaemia in animal models of type 1 diabetes. Within humans with type 1 diabetes, exposure to glycaemic extremes has been associated with alterations in hippocampal structure and in memory function, but results are inconsistent. It has been hypothesised that the effects of hypoglycaemia and hyperglycaemia on the hippocampus may depend on when during neurodevelopment these extremes occur, possibly explaining some of these inconsistencies. However, data addressing this concept are limited. We review here the existing literature on this complex topic and suggest future avenues of required research.

Acute changes in mood induced by subthalamic deep brain stimulation in Parkinson disease are modulated by psychiatric diagnosis.

BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN DBS) reduces Parkinson disease (PD) motor symptoms but has unexplained, variable effects on mood. OBJECTIVE: The study tested the hypothesis that pre-existing mood and/or anxiety disorders or increased symptom severity negatively affects mood response to STN DBS. METHODS: Thirty-eight PD participants with bilateral STN DBS and on PD medications were interviewed with Structured Clinical Interview for DSM-IV-TR Axis I Disorders (SCID) and completed Beck Depression Inventory (BDI) and Spielberger State Anxiety Inventory (SSAI) self-reports. Subsequently, during OFF and optimal ON (clinical settings) STN DBS conditions and while off PD medications, motor function was assessed with the United Parkinson Disease Rating Scale (UPDRS, part III), and participants rated their mood with Visual Analogue Scales (VAS), and again completed SSAI. VAS mood variables included anxiety, apathy, valence and emotional arousal. RESULTS: STN DBS improved UPDRS scores and mood. Unexpectedly, PD participants diagnosed with current anxiety or mood disorders experienced greater STN DBS-induced improvement in mood than those diagnosed with remitted disorders or who were deemed as having never met threshold criteria for diagnosis. BDI and SSAI scores did not modulate mood response to STN DBS, indicating that clinical categorical diagnosis better differentiates mood response to STN DBS than self-rated symptom severity. SCID diagnosis, BDI and SSAI scores did not modulate motor response to STN DBS. CONCLUSIONS: PD participants diagnosed with current mood or anxiety disorders are more sensitive to STN DBS-induced effects on mood, possibly indicating altered basal ganglia circuitry in this group.

Early brain vulnerability in Wolfram syndrome.

Wolfram Syndrome (WFS) is a rare autosomal recessive disease characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, diabetes insipidus, deafness, and neurological dysfunction leading to death in mid-adulthood. WFS is caused by mutations in the WFS1 gene, which lead to endoplasmic reticulum (ER) stress-mediated cell death. Case studies have found widespread brain atrophy in late stage WFS. However, it is not known when in the disease course these brain abnormalities arise, and whether there is differential vulnerability across brain regions and tissue classes. To address this limitation, we quantified regional brain abnormalities across multiple imaging modalities in a cohort of young patients in relatively early stages of WFS. Children and young adults with WFS were evaluated with neurological, cognitive and structural magnetic resonance imaging measures. Compared to normative data, the WFS group had intact cognition, significant anxiety and depression, and gait abnormalities. Compared to healthy and type 1 diabetic control groups, the WFS group had smaller intracranial volume and preferentially affected gray matter volume and white matter microstructural integrity in the brainstem, cerebellum and optic radiations. Abnormalities were detected in even the youngest patients with mildest symptoms, and some measures did not follow the typical age-dependent developmental trajectory. These results establish that WFS is associated with smaller intracranial volume with specific abnormalities in the brainstem and cerebellum, even at the earliest stage of clinical symptoms. This pattern of abnormalities suggests that WFS has a pronounced impact on early brain development in addition to later neurodegenerative effects, representing a significant new insight into the WFS disease process. Longitudinal studies will be critical for confirming and expanding our understanding of the impact of ER stress dysregulation on brain development.

Prospectively determined impact of type 1 diabetes on brain volume during development.

OBJECTIVE: The impact of type 1 diabetes mellitus (T1DM) on the developing central nervous system is not well understood. Cross-sectional, retrospective studies suggest that exposure to glycemic extremes during development is harmful to brain structure in youth with T1DM. However, these studies cannot identify brain regions that change differentially over time depending on the degree of exposure to glycemic extremes. RESEARCH DESIGN AND METHODS: We performed a longitudinal, prospective structural neuroimaging study of youth with T1DM (n = 75; mean age = 12.5 years) and their nondiabetic siblings (n = 25; mean age = 12.5 years). Each participant was scanned twice, separated by 2 years. Blood glucose control measurements (HbA(1c), glucose meter results, and reports of severe hypoglycemia) were acquired during the 2-year follow-up. Sophisticated image registration algorithms were performed, followed by whole brain and voxel-wise statistical analyses of the change in gray and white matter volume, controlling for age, sex, and age of diabetes onset. RESULTS: The T1DM and nondiabetic control (NDC) sibling groups did not differ in whole brain or voxel-wise change over the 2-year follow-up. However, within the T1DM group, participants with more hyperglycemia had a greater decrease in whole brain gray matter compared with those with less hyperglycemia (P < 0.05). Participants who experienced severe hypoglycemia had greater decreases in occipital/parietal white matter volume compared with those with no severe hypoglycemia (P < 0.05) and compared with the NDC sibling group (P < 0.05). CONCLUSIONS: These results demonstrate that within diabetes, exposure to hyperglycemia and severe hypoglycemia may result in subtle deviation from normal developmental trajectories of the brain.

Functional neuroanatomy of lexical processing in children with cleft lip and palate.

BACKGROUND: Patients with palatal clefts are predisposed to developing speech and language abnormalities. Emerging evidence indicates that children with cleft lip and/or cleft palate have higher rates of learning disabilities than the general population and differences in brain morphology. METHODS: Magnetic resonance imaging of 12 individuals with isolated unilateral complete clefts of the lip and palate produced functional images during three lexical processing tasks: generation of verbs, opposites, and rhymes. Direct statistical comparisons were made between subjects with cleft lip and palate and controls (matched for age and performance) from an extant data set, both as a group and individually. RESULTS: Two types of differences were found. Compared with unaffected controls, subjects with clefts showed a delayed and elongated blood oxygen level-dependent response in regions found throughout the cerebrum, including in the prefrontal cortex, cingulate gyrus, right precuneus, and right temporal gyrus. A right middle frontal gyrus region was activated by these tasks in controls but not in subjects with clefts. Developmental analysis showed that subjects 14.5 years and older (n = 5) had a larger number of age-related regions differing in blood oxygen level-dependent response from controls than did younger subjects (n = 7). Single-patient analysis demonstrated substantial individual variability. CONCLUSIONS: Children with cleft lip and palate, performing lexical processing tasks at a comparable level of proficiency, use a similar but nonidentical functional neuroanatomy than peers without clefts. Differing neural circuitry for language tasks and differing developmental trajectories could help explain the predisposition to velopharyngeal dysfunction and learning disabilities in this population.

The development of sustained and transient neural activity.

Sustained and transient signals were compared in a group of 7-8-year-old children and a group of adults performing the same cognitive task using functional magnetic resonance imaging (fMRI) in conjunction with a mixed blocked/event-related design. Results revealed several regions, including a region in the right lateral inferior frontal gyrus, that exhibited opposing developmental trajectories in sustained and transient signals--in particular, decreased sustained signals and increased transient signals with age. Re-analysis of the data assuming "blocked" and "event-related" designs, as opposed to a mixed design, produced different results. In combination, these results may help to explain contradictory findings in the literature regarding the direction of neural development in frontal cortex. Moreover, these results underscore the value of separating sustained and transient signals in fMRI studies of development.

Task demands modulate sustained and transient neural activity during visual-matching tasks.

The extent to which a task demands verbal or non-verbal processing may influence which neural regions underlie performance. In the present study, sustained and transient responses were examined using functional magnetic resonance imaging (fMRI) in conjunction with a mixed blocked/event-related design during three visual-matching tasks that varied in the extent to which they relied on verbal processing. In a name-matching task, subjects decided whether two letters had the same or a different name (e.g., A a); in a physical-matching task, subjects decided whether two letters were exactly the same or different (e.g., A A); in a non-letter-matching task, subjects decided whether two non-letters were exactly the same or different. Results revealed several regions in which sustained activity differed across the three tasks as well as several regions in which sustained activity did not differ. Most notably, regions in the right inferior frontal gyrus exhibited greater sustained activity during the name-matching task than during the physical or non-letter-matching tasks, indicating that sustained activity in this region is sensitive to the amount of verbal processing required by a particular task. Moreover, transient activity in the right inferior frontal regions, as well as others, exhibited the opposite pattern of results. In combination, results suggest that sustained and transient activities interact to produce the context-appropriate response during visual-matching tasks.

Developmental changes in human cerebral functional organization for word generation.

A fundamental issue in cognitive neuroscience is the nature of developmental changes in human cerebral functional organization for higher cognitive functions. Event-related functional magnetic resonance imaging was used to measure developmental changes in the functional neuroanatomy subserving controlled lexical association. First, brain regions showing significant differences in activity between school-age children and young adults, despite equivalent task performance, were identified. Then, activity in these regions was more fully characterized in individuals spanning the ages of 7-32 years old. Cross-sectional and regression analyses showed systematic increases and decreases in levels of activity over age, by region. Age-related increases in activity were primarily newly recruited, later-stage processing regions, such as in left frontal and left parietal cortex. Decreases, on the other hand, were all positive activations that attenuated with age and were found across a wider neuroanatomical range, including earlier processing regions such as bilateral extrastriate cortex. The hemodynamic magnitude, neuroanatomical location and maturational timecourse of these progressive and regressive changes have implications for models of the developing specialization in human cerebral functional organization.

Sustained and transient activity during an object-naming task: a mixed blocked and event-related fMRI study.

Cognitive tasks often involve at least two types of processes-sustained processes potentially related to ongoing task demands and transient processes related to the processing of individual items within the task. Using functional magnetic resonance imaging, in conjunction with a mixed-blocked and event-related design, we examined sustained and transient patterns of neural activity during an object-naming task. Subjects were imaged during runs that alternated between control blocks and task blocks. During task blocks, primed and unprimed objects were intermixed and jittered in time. Regions of interest based on separate analyses of sustained and transient activities were tested independently for sustained and transient responses. Three general patterns of results were observed. (1) Some regions exhibited transient responses but little or no sustained response. These regions were widely distributed across the brain. (2) Other regions clearly exhibited both transient and sustained responses. These regions were found primarily in lateral and medial frontal lobes. (3) A few regions exhibited a sustained response but little or no transient responses. These regions were found in the basal ganglia, orbitofrontal lobe, and right lateral frontal lobe. Furthermore, two homotopic regional pairs in the right and left inferior frontal lobe (frontal operculum and inferior frontal cortex) showed a crossover of sustained and transient effects, with greater transient activity in the left and greater sustained activity in the right hemisphere. The asymmetric relationship between sustained and transient responses in prefrontal regions may be an example of task-specific biasing at work.

Functional neuroanatomical differences between adults and school-age children in the processing of single words.

A critical issue in developmental cognitive neuroscience is the extent to which the functional neuroanatomy underlying task performance differs in adults and children. Direct comparisons of brain activation in the left frontal and extrastriate cortex were made in adults and children (aged 7 to 10 years) performing single-word processing tasks with visual presentation; differences were found in circumscribed frontal and extrastriate regions. Conceivably, these differences could be attributable exclusively to performance discrepancies; alternatively, maturational differences in functional neuroanatomy could exist despite similar performance. Some of the brain regions examined showed differences attributable to age independent of performance, suggesting that maturation of the pattern of regional activations for these tasks is incomplete at age 10.