Robert K Fulbright

Haskins Laboratories, New Haven, Connecticut, United States

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Publications (129)636.15 Total impact

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    ABSTRACT: Despite anecdotal evidence of relative visuospatial processing strengths in individuals with reading disability (RD), only a few studies have assessed the presence or the extent of these putative strengths. The current study examined the cognitive and neural bases of visuospatial processing abilities in adolescents with RD relative to typically developing (TD) peers. Using both cognitive tasks and functional magnetic resonance imaging (fMRI) we contrasted printed word recognition with non-language visuospatial processing tasks. Behaviorally, lower reading skill was related to a visuospatial processing advantage (shorter latencies and equivalent accuracy) on a geometric figure processing task, similar to findings shown in two published studies. FMRI analyses revealed key group by task interactions in patterns of cortical and subcortical activation, particularly in frontostriatal networks, and in the distributions of right and left hemisphere activation on the two tasks. The results are discussed in terms of a possible neural tradeoff in visuospatial processing in RD.
    NeuroImage 07/2014; · 6.25 Impact Factor
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    ABSTRACT: Reading disability is a brain-based difficulty in acquiring fluent reading skills that affects significant numbers of children. Although neuroanatomical and neurofunctional networks involved in typical and atypical reading are increasingly well characterized, the underlying neurochemical bases of individual differences in reading development are virtually unknown. The current study is the first to examine neurochemistry in children during the critical period in which the neurocircuits that support skilled reading are still developing. In a longitudinal pediatric sample of emergent readers whose reading indicators range on a continuum from impaired to superior, we examined the relationship between individual differences in reading and reading-related skills and concentrations of neurometabolites measured using magnetic resonance spectroscopy. Both continuous and group analyses revealed that choline and glutamate concentrations were negatively correlated with reading and related linguistic measures in phonology and vocabulary (such that higher concentrations were associated with poorer performance). Correlations with behavioral scores obtained 24 months later reveal stability for the relationship between glutamate and reading performance. Implications for neurodevelopmental models of reading and reading disability are discussed, including possible links of choline and glutamate to white matter anomalies and hyperexcitability. These findings point to new directions for research on gene-brain-behavior pathways in human studies of reading disability.
    Journal of Neuroscience 03/2014; 34(11):4082-9. · 6.91 Impact Factor
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    ABSTRACT: The purpose of the study was to identify structural brain differences in school-age children with residual speech sound errors. Voxel based morphometry was used to compare gray and white matter volumes for 23 children with speech sound errors, ages 8;6-11;11, and 54 typically speaking children matched on age, oral language, and IQ. We hypothesized that regions associated with production and perception of speech sounds would differ between groups. Results indicated greater gray matter volumes for the speech sound error group relative to typically speaking controls in bilateral superior temporal gyrus. There was greater white matter volume in the corpus callosum for the speech sound error group, but less white matter volume in right lateral occipital gyrus. Results may indicate delays in neuronal pruning in critical speech regions or differences in the development of networks for speech perception and production.
    Brain and Language 12/2013; 128(1):25-33. · 3.39 Impact Factor
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    ABSTRACT: PURPOSE: BECTS (benign epilepsy with centro-temporal spikes) is one of the most common childhood-onset epilepsy syndromes. We investigated quantitative evidence for brain morphological variation associated with BECTS to provide insights into the neuroanatomical basis of this disorder. METHODS: Three independent BECTS groups were imaged at different stages: (a) near onset (n=16, mean age 9.3±1.6 years), (b) ∼9 years after onset (n=9, mean age 15.8±2.3 years), and (c) ∼15 years after onset (n=10, mean age 22.7±2.7 years). Age-matched controls were imaged with each group. Whole brain T1-weighted MRI was acquired. Voxel-based morphometry (groups a-c) and cortical thickness analyses (groups b and c) were undertaken within each group and for the groups combined. The relationship between cortical morphology and age was investigated. KEY FINDINGS: The voxel-based morphometry analysis indicated increased bilateral grey matter volume in the superior frontal gyrus, insula and right inferior frontal gyrus regions in BECTS. The magnitude of the increase lessened with age of the cases. Cortical thickness analysis revealed thicker cortex in BECTS along middle and inferior frontal gyri bilaterally, left insula and bilateral supramarginal gyrus in the 9-year-after-onset group, that normalised with age. The rate of cortical thickness changes with age were greater in BECTS cases than in controls. SIGNIFICANCE: Increased cortical gray matter associated with BECTS was found. The decreasing magnitude of the effect with increasing age parallels the natural history of the disorder. The areas affected are consistent with neurocognitive dysfunction in BECTS.
    Epilepsy research 01/2013; · 2.48 Impact Factor
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    ABSTRACT: Rodent (13)C magnetic resonance spectroscopy studies show that glutamatergic signaling requires high oxidative energy in the awake resting state and allowed calibration of functional magnetic resonance imaging (fMRI) signal in terms of energy relative to the resting energy. Here, we derived energy used for glutamatergic signaling in the awake resting human. We analyzed human data of electroencephalography (EEG), positron emission tomography (PET) maps of oxygen (CMR(O2)) and glucose (CMR(glc)) utilization, and calibrated fMRI from a variety of experimental conditions. CMR(glc) and EEG in the visual cortex were tightly coupled over several conditions, showing that the oxidative demand for signaling was four times greater than the demand for nonsignaling events in the awake state. Variations of CMR(O2) and CMR(glc) from gray-matter regions and networks were within ±10% of means, suggesting that most areas required similar energy for ubiquitously high resting activity. Human calibrated fMRI results suggest that changes of fMRI signal in cognitive studies contribute at most ±10% CMR(O2) changes from rest. The PET data of sleep, vegetative state, and anesthesia show metabolic reductions from rest, uniformly >20% across, indicating no region is selectively reduced when consciousness is lost. Future clinical investigations will benefit from using quantitative metabolic measures.Journal of Cerebral Blood Flow & Metabolism advance online publication, 9 January 2013; doi:10.1038/jcbfm.2012.207.
    Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism 01/2013; · 5.46 Impact Factor
  • Joachim M Baehring, Robert K Fulbright
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    ABSTRACT: SUMMARY Diffusion-weighted MRI (DW-MRI) provides image contrast dependent on the molecular movement of water. It has been most widely used in the diagnosis of cytotoxic edema secondary to acute cerebral ischemia, but has also proven useful in assessing tumor cellularity and grade, abscess formation, cysts and various forms of white matter disorders. Furthermore, DW-MRI is used to generate maps of subcortical white matter tracts and their relationship to structural brain lesions that may serve for preoperative planning and intraoperative guidance. We provide a comprehensive review of current practical applications of DW-MRI in the diagnosis and treatment of primary brain tumors, metastases and nonmetastatic neurologic complications of cancer. A detailed description of diffusion tensor imaging is beyond the scope of this review. We performed a comprehensive search of the PubMed database of the USA National Library of Medicine with use of various combinations of the following search terms: diffusion-weighted imaging, apparent diffusion coefficient, diffusion tensor imaging, diffusion tensor, brain, tumor, glioblastoma, lymphoma, primary CNS lymphoma, stroke, cancer, abscess, leukoencephalopathy, methotrexate, fluorouracil, capecitabine. We identified original articles and well-documented case reports of DW-MRI applications in patients with primary brain neoplasms, metastases and nonmetastatic neurologic complications that we judged to be of high impact on the field. We largely selected publications from the past 10 years, but did not exclude commonly referenced and highly regarded older publications. We also searched the reference lists of articles identified by this search strategy and selected those we judged relevant. Review articles are cited to provide readers with more details and more references than can be covered here.
    CNS oncology. 11/2012; 1(2):155-167.
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    ABSTRACT: Preterm (PT) subjects are at risk for developmental delay, and task-based studies suggest that developmental disorders may be due to alterations in neural connectivity. Since emerging data imply the importance of right cerebellar function for language acquisition in typical development, we hypothesized that PT subjects would have alternate areas of cerebellar connectivity, and that these areas would be responsible for differences in cognitive outcomes between PT subjects and term controls at age 20years. Nineteen PT and 19 term control young adults were prospectively studied using resting-state functional MRI (fMRI) to create voxel-based contrast maps reflecting the functional connectivity of each tissue element in the grey matter through analysis of the intrinsic connectivity contrast degree (ICC-d). Left cerebellar ICC-d differences between subjects identified a region of interest that was used for subsequent seed-based connectivity analyses. Subjects underwent standardized language testing, and correlations with cognitive outcomes were assessed. There were no differences in gender, hand preference, maternal education, age at study, or Peabody Picture Vocabulary Test (PPVT) scores. Functional connectivity (FcMRI) demonstrated increased tissue connectivity in the biventer, simple and quadrangular lobules of the L cerebellum (p<0.05) in PTs compared to term controls; seed-based analyses from these regions demonstrated alterations in connectivity from L cerebellum to both R and L inferior frontal gyri (IFG) in PTs compared to term controls. For PTs but not term controls, there were significant positive correlations between these connections and PPVT scores (R IFG: r=0.555, p=0.01; L IFG: r=0.454, p=0.05), as well as Verbal Comprehension Index (VCI) scores (R IFG: r=0.472, p=0.04). These data suggest the presence of a left cerebellar language circuit in PT subjects at young adulthood. These findings may represent either a delay in maturation or the engagement of alternative neural pathways for language in the developing PT brain.
    NeuroImage 09/2012; 64C:371-378. · 6.25 Impact Factor
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    ABSTRACT: Reading disability (RD) is a complex genetic disorder with unknown etiology. Genes on chromosome 6p22, including DCDC2, KIAA0319, and TTRAP, have been identified as RD associated genes. Imaging studies have shown both functional and structural differences between brains of individuals with and without RD. There are limited association studies performed between RD genes, specifically genes on 6p22, and regional brain activation during reading tasks. Using fourteen variants in DCDC2, KIAA0319, and TTRAP and exhaustive reading measures, we first tested for association with reading performance in 82 parent-offspring families (326 individuals). Next, we determined the association of these variants with activation of sixteen brain regions of interest during four functional magnetic resonance imaging-reading tasks. We nominally replicated associations between reading performance and variants of DCDC2 and KIAA0319. Furthermore, we observed a number of associations with brain activation patterns during imaging-reading tasks with all three genes. The strongest association occurred between activation of the left anterior inferior parietal lobe and complex tandem repeat BV677278 in DCDC2 (uncorrected p=0.00003, q=0.0442). Our results show that activation patterns across regions of interest in the brain are influenced by variants in the DYX2 locus. The combination of genetic and functional imaging data show a link between genes and brain functioning during reading tasks in subjects with RD. This study highlights the many advantages of imaging data as an endophenotype for discerning genetic risk factors for RD and other communication disorders and underscores the importance of integrating neurocognitive, imaging, and genetic data in future investigations.
    NeuroImage 06/2012; 63(1):148-56. · 6.25 Impact Factor
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    ABSTRACT: We employed brain-behavior analyses to explore the relationship between performance on tasks measuring phonological awareness, pseudoword decoding, and rapid auditory processing (all predictors of reading (dis)ability) and brain organization for print and speech in beginning readers. For print-related activation, we observed a shared set of skill-correlated regions, including left hemisphere temporoparietal and occipitotemporal sites, as well as inferior frontal, visual, visual attention, and subcortical components. For speech-related activation, shared variance among reading skill measures was most prominently correlated with activation in left hemisphere inferior frontal gyrus and precuneus. Implications for brain-based models of literacy acquisition are discussed.
    Brain and Language 05/2012; · 3.39 Impact Factor
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    ABSTRACT: Although stress and drug cue exposure each increase drug craving and contribute to relapse in cocaine dependence, no previous research has directly examined the neural correlates of stress-induced and drug cue-induced craving in cocaine-dependent women and men relative to comparison subjects. Functional MRI was used to assess responses to individualized scripts for stress, drug/alcohol cue and neutral-relaxing-imagery conditions in 30 abstinent cocaine-dependent individuals (16 women, 14 men) and 36 healthy recreational-drinking comparison subjects (18 women, 18 men). Significant three-way interactions between diagnostic group, sex, and script condition were observed in multiple brain regions including the striatum, insula, and anterior and posterior cingulate. Within women, group-by-condition interactions were observed involving these regions and were attributable to relatively increased regional activations in cocaine-dependent women during the stress and, to a lesser extent, neutral-relaxing conditions. Within men, group main effects were observed involving these same regions, with cocaine-dependent men demonstrating relatively increased activation across conditions, with the main contributions from the drug and neutral-relaxing conditions. In men and women, subjective drug-induced craving measures correlated positively with corticostriatal-limbic activations. In cocaine dependence, corticostriatal-limbic hyperactivity appears to be linked to stress cues in women, drug cues in men, and neutral-relaxing conditions in both. These findings suggest that sex should be taken into account in the selection of therapies in the treatment of addiction, particularly those targeting stress reduction.
    American Journal of Psychiatry 01/2012; 169(4):406-14. · 14.72 Impact Factor
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    ABSTRACT: To examine neural response to spoken and printed language in children with speech sound errors (SSE). Functional magnetic resonance imaging was used to compare processing of auditorily and visually presented words and pseudowords in 17 children with SSE, ages 8;6[years;months] through 10;10, with 17 matched controls. When processing spoken words and pseudowords, the SSE group showed less activation than typically speaking controls in left middle temporal gyrus. They also showed greater activation than controls in several cortical and subcortical regions (e.g., left superior temporal gyrus, globus pallidus, insula, fusiform, and bilateral parietal regions). In response to printed words and pseudowords, children with SSE had greater activation than controls in regions including bilateral fusiform and anterior cingulate. Some differences were found in both speech and print processing that that may be associated with children with SSE failing to show common patterns of task-induced deactivation and/or attentional resource allocation. Compared with controls, children with SSE appear to rely more on several dorsal speech perception regions and less on ventral speech perception regions. When processing print, numerous regions were observed to be activated more for the SSE group than for controls.
    Journal of Speech Language and Hearing Research 01/2012; 55(4):1068-82. · 1.97 Impact Factor
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    ABSTRACT: This magnetic resonance imaging study demonstrates increased lateral ventricle volume (LVV) in adolescents and adults with bipolar disorder (BD) with psychotic symptoms, but not without psychosis, compared to healthy adolescents and adults. This suggests LVV is a morphologic feature associated with psychosis in BD, present by adolescence.
    Psychiatry Research 12/2011; 194(3):400-2. · 2.68 Impact Factor
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    ABSTRACT: Potocki-Lupski syndrome (PTLS; OMIM 610883) is a genomic syndrome that arises as a result of a duplication of 17p11.2. Although numerous cases of individuals with PTLS have been presented in the literature, its behavioral characterization is still ambiguous. We present a male child with a de novo dup(17)(p11.2p11.2) and he does not possess any autistic features, but is characterized by severe speech and language impairment. In the context of the analyses of this patient and other cases of PTLS, we argue that the central feature of the syndrome appears to be related to diminished speech and language capacity, rather than the specific social deficits central to autism.
    Brain & development 12/2011; 34(8):700-3. · 1.74 Impact Factor
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    ABSTRACT: Abstract Objective. Magnetic resonance imaging (MRI) studies have demonstrated functional prefrontal cortical (PFC) abnormalities in pathological gambling (PG) and other psychiatric disorders characterized by impaired impulse control; e.g., cocaine dependence and bipolar disorder. These abnormalities are accompanied by impairments in white matter microstructures in the anterior (genual) corpus callosum (CC) in cocaine dependence and bipolar disorder. Prior studies have not examined white matter integrity in PG. We predicted impairments in genual CC white matter in PG. Methods. Nineteen participants with PG and 19 matched control participants underwent diffusion tensor imaging (DTI) to compare white matter integrity in the CC, as assessed using fractional anisotropy (FA). Results. In PG subjects as compared to control subjects, reduced FA values in the left and right genu of the CC were observed. Multiple regression analyses confirmed that PG status - in addition to age and past alcohol abuse/dependence (AA/AD) - was a significant predictor of genual FA values. Among PG participants, left and right genu FA values were negatively correlated with scores on the Behavioral Activation System Fun-Seeking (BAS-FS) subscale. Limitations. Limitations include a reliance on self-report measures of impulsivity and related constructs and a relatively small sample of PG subjects with past AA/AD. Conclusion. Findings of decreased FA values in the genu of the CC in PG subjects suggest that, like with other disorders of behavioral dyscontrol, white matter microstructural abnormalities contribute to the pathophysiology of PG. These differences appear particularly relevant to individuals with remitted AA/AD, highlighting the importance of considering co-occurring substance use disorders when investigating PG.
    The World Journal of Biological Psychiatry 05/2011; · 3.57 Impact Factor
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    ABSTRACT: Epidemiologic evidence suggests the natural history of refractory mesial temporal lobe epilepsy is complicated, yet little is known about the hippocampus from the nontertiary center perspective. In a community-based cohort, individuals with nonsyndromic focal epilepsy with onset <16 years and controls had research MRI scans. Hippocampal (HC) volumes were manually measured, corrected for total brain volume, and converted to Z scores (Z(HC)) based on the controls' values. Volumes in cases and controls were compared. Average volumes were not significantly different in cases with unknown cause (n = 117) relative to controls (n = 63). The group with structural and other conditions (n = 23) had significantly smaller volumes. Asymmetry (larger/smaller HC) did not vary among the 3 groups. Hippocampal variances were significantly larger in each epilepsy group relative to controls. In the unknown cause group, 25 (21%) had extreme() values: 15 (13%) with Z(HC) >1.96; 10 (9%) with Z(HC) <-1.96. By contrast, 2/63 (3%) controls had extreme values (p = 0.001). Within the unknown cause group, temporal lobe epilepsy (TLE) cases were more likely to have extreme hippocampal volumes than non-TLE (31% vs 15%, p = 0.03). Extreme volumes were generally interpreted as normal visually. These anomalies were not associated with seizure remission or pharmacoresistance. Classic mesial TLE with hippocampal sclerosis is an uncommon finding in the general population. Volume anomalies, both large and small, are often bilateral. The significance of these findings is unclear; however, speculations regarding preexisting hippocampal pathology (e.g., dysplasia) as a factor in TLE and other neocortical epilepsies have been made by others.
    Neurology 04/2011; 76(16):1415-21. · 8.25 Impact Factor
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    ABSTRACT: We present new evidence based on fMRI for the existence and neural architecture of an abstract supramodal language system that can integrate linguistic inputs arising from different modalities such that speech and print each activate a common code. Working with sentence material, our aim was to find out where the putative supramodal system is located and how it responds to comprehension challenges. To probe these questions we examined BOLD activity in experienced readers while they performed a semantic categorization task with matched written or spoken sentences that were either well-formed or contained anomalies of syntactic form or pragmatic content. On whole-brain scans, both anomalies increased net activity over non-anomalous baseline sentences, chiefly at left frontal and temporal regions of heteromodal cortex. The anomaly-sensitive sites correspond approximately to those that previous studies (Michael et al., 2001; Constable et al., 2004) have found to be sensitive to other differences in sentence complexity (object relative minus subject relative). Regions of interest (ROIs) were defined by peak response to anomaly averaging over modality conditions. Each anomaly-sensitive ROI showed the same pattern of response across sentence types in each modality. Voxel-by-voxel exploration over the whole brain based on a cosine similarity measure of common function confirmed the specificity of supramodal zones.
    Cortex 04/2011; 47(4):416-31. · 6.16 Impact Factor
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    ABSTRACT: We provide an illustration of an application of the elastic net to a large number of common genetic variants in the context of the search for the genetic bases of an endophenotype conceivably related to individual differences in learning. GABA concentration in the occipital cortex, a critical area for reading, was obtained in a group (n = 76) of children aged 6-10 years. Two extreme groups, high and low, were selected for genotyping with the 650Y Illumina array chip (Ilmn650Y). An elastic net approach was applied to the resulting SNP dataset; 100 SNPs were identified for each chromosome as "interesting" based on having the highest absolute value coefficients. The analyses highlighted chromosomes 15 and 20, which contained 55 candidate genes. The STRING partner analyses of the associated proteins pointed to a number of related genes, most notably, GABA and NTRK receptors.
    Behavior Genetics 01/2011; 41(1):120-4. · 2.61 Impact Factor
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    ABSTRACT: Early language development sets the stage for a lifetime of competence in language and literacy. However, the neural mechanisms associated with the relative advantages of early communication success, or the disadvantages of having delayed language development, are not well explored. In this study, 174 elementary school-age children whose parents reported that they started forming sentences 'early', 'on-time' or 'late' were evaluated with standardized measures of language, reading and spelling. All oral and written language measures revealed consistent patterns for 'early' talkers to have the highest level of performance and 'late' talkers to have the lowest level of performance. We report functional magnetic resonance imaging data from a subset of early, on-time and late talkers matched for age, gender and performance intelligence quotient that allows evaluation of neural activation patterns produced while listening to and reading real words and pronounceable non-words. Activation in bilateral thalamus and putamen, and left insula and superior temporal gyrus during these tasks was significantly lower in late talkers, demonstrating that residual effects of being a late talker are found not only in behavioural tests of oral and written language, but also in distributed cortical-subcortical neural circuits underlying speech and print processing. Moreover, these findings suggest that the age of functional language acquisition can have long-reaching effects on reading and language behaviour, and on the corresponding neurocircuitry that supports linguistic function into the school-age years.
    Brain 08/2010; 133(Pt 8):2185-95. · 9.92 Impact Factor
  • Medical Physics 01/2010; 37(6). · 2.91 Impact Factor
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    ABSTRACT: This paper addresses the problem of indexing shapes in medical image databases. Shapes of organs are often indicative of disease, making shape similarity queries important in medical image databases. Mathematically, shapes with landmarks belong to shape spaces which are curved manifolds with a well defined metric. The challenge in shape indexing is to index data in such curved spaces. One natural indexing scheme is to use metric trees, but metric trees are prone to inefficiency. This paper proposes a more efficient alternative. We show that it is possible to optimally embed finite sets of shapes in shape space into a Euclidean space. After embedding, classical coordinate-based trees can be used for efficient shape retrieval. The embedding proposed in the paper is optimal in the sense that it least distorts the partial Procrustes shape distance. The proposed indexing technique is used to retrieve images by vertebral shape from the NHANES II database of cervical and lumbar spine X-ray images maintained at the National Library of Medicine. Vertebral shape strongly correlates with the presence of osteophytes, and shape similarity retrieval is proposed as a tool for retrieval by osteophyte presence and severity. Experimental results included in the paper evaluate (1) the usefulness of shape similarity as a proxy for osteophytes, (2) the computational and disk access efficiency of the new indexing scheme, (3) the relative performance of indexing with embedding to the performance of indexing without embedding, and (4) the computational cost of indexing using the proposed embedding versus the cost of an alternate embedding. The experimental results clearly show the relevance of shape indexing and the advantage of using the proposed embedding.
    Medical image analysis 01/2010; 14(3):243-54. · 3.09 Impact Factor

Publication Stats

7k Citations
636.15 Total Impact Points

Institutions

  • 1999–2012
    • Haskins Laboratories
      New Haven, Connecticut, United States
  • 1993–2012
    • Yale-New Haven Hospital
      • Department of Laboratory Medicine
      New Haven, Connecticut, United States
  • 1993–2010
    • Yale University
      • • Department of Electrical Engineering
      • • Haskins Laboratories
      • • Department of Neurology
      • • Department of Diagnostic Radiology and Pediatric Diagnostic Radiology
      • • Department of Psychiatry
      • • Department of Pediatrics
      New Haven, CT, United States
  • 2008
    • University of Connecticut
      • Department of Psychology
      Mansfield City, CT, United States
  • 1998
    • University of Rochester
      • School of Medicine and Dentistry
      Rochester, NY, United States