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ABSTRACT: The presence of a photopigment (melanopsin) within certain retinal ganglion cells was a surprising and significant discovery. This pigment is routinely described as "nonvisual" to highlight its signaling role in pupil dilation and circadian rhythms. Here we asked whether light absorbed by melanopsin can be seen by healthy human subjects. To answer this requires delivering intense (above rod saturation), well-controlled lights using four independent primaries. We collected detection thresholds to many four-primary stimuli. Threshold measurements in the fovea are explained by trichromatic theory, with no need to invoke a fourth photopigment. In the periphery, where melanopsin is present, threshold measurements deviate from trichromatic theory; at high photopic levels, sensitivity is explained by absorptions in four, not three, photopigment classes. We consider a series of hypotheses to explain the tetrasensitivity at high photopic levels in the human peripheral field. The most likely hypothesis is that in healthy human subjects melanopsin absorptions influence visibility.
Proceedings of the National Academy of Sciences 12/2012; · 9.68 Impact Factor
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ABSTRACT: White matter tissue properties are highly correlated with reading proficiency; we would like to have a model that relates
the dynamics of an individual’s white matter development to their acquisition of skilled reading. The development of cerebral
white matter involves multiple biological processes, and the balance between these processes differs between individuals.
Cross-sectional measures of white matter mask the interplay between these processes and their connection to an individual’s
cognitive development. Hence, we performed a longitudinal study to measure white-matter development (diffusion-weighted imaging)
and reading development (behavioral testing) in individual children (age 7–15 y). The pattern of white-matter development
differed significantly among children. In the left arcuate and left inferior longitudinal fasciculus, children with above-average
reading skills initially had low fractional anisotropy (FA) that increased over the 3-y period, whereas children with below-average
reading skills had higher initial FA that declined over time. We describe a dual-process model of white matter development
comprising biological processes with opposing effects on FA, such as axonal myelination and pruning, to explain the pattern
of results.
Proceedings of the National Academy of Sciences 10/2012; 109(44):E3045-E3053. · 9.68 Impact Factor
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ABSTRACT: Memory loss is often the first and most prominent symptom of Alzheimer's disease (AD), coinciding with the spread of neurofibrillary pathology from the entorhinal cortex (ERC) to the hippocampus. The apical dendrites of hippocampal CA1 pyramidal neurons, in the stratum radiatum/stratum lacunosum-moleculare (SRLM), are among the earliest targets of this pathology, and atrophy of the CA1-SRLM is apparent in postmortem tissue from patients with mild AD. We previously demonstrated that CA1-SRLM thinning is also apparent in vivo, using ultra-high field 7-Tesla (7T) MRI to obtain high-resolution hippocampal microstructural imaging. Here, we hypothesized that CA1-SRLM thickness would correlate with episodic memory performance among patients with mild AD. We scanned nine patients, using an oblique coronal T2-weighted sequence through the hippocampal body with an in-plane resolution of 220 μm, allowing direct visual identification of subfields - dentate gyrus (DG)/CA3, CA2, CA1, and ERC - and hippocampal strata - SRLM and stratum pyramidale (SP). We present a novel semi-automated method of measuring stratal width that correlated well with manual measurements. We performed multi-domain neuropsychological evaluations that included three tests of episodic memory, yielding composite scores for immediate recall, delayed recall, and delayed recognition memory. Strong correlations occurred between delayed recall performance and the widths of CA1-SRLM (r(2)=0.69; p=0.005), CA1-SP (r(2)=0.5; p=0.034), and ERC (r(2)=0.62; p=0.012). The correlation between CA1-SRLM width and delayed recall lateralized to the left hemisphere. DG/CA3 size did not correlate significantly with any aspect of memory performance. These findings highlight a role for 7T hippocampal microstructural imaging in revealing focal structural pathology that correlates with the central cognitive feature of AD.
NeuroImage 07/2012; 63(1):194-202. · 5.89 Impact Factor
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ABSTRACT: Frontostriatal circuits have been implicated in reward learning, and emerging findings suggest that frontal white matter structural integrity and probabilistic reward learning are reduced in older age. This cross-sectional study examined whether age differences in frontostriatal white matter integrity could account for age differences in reward learning in a community life span sample of human adults. By combining diffusion tensor imaging with a probabilistic reward learning task, we found that older age was associated with decreased reward learning and decreased white matter integrity in specific pathways running from the thalamus to the medial prefrontal cortex and from the medial prefrontal cortex to the ventral striatum. Further, white matter integrity in these thalamocorticostriatal paths could statistically account for age differences in learning. These findings suggest that the integrity of frontostriatal white matter pathways critically supports reward learning. The findings also raise the possibility that interventions that bolster frontostriatal integrity might improve reward learning and decision making.
Journal of Neuroscience 04/2012; 32(15):5333-7. · 7.11 Impact Factor
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ABSTRACT: Tractography based on diffusion weighted imaging (DWI) data is a method for identifying the major white matter fascicles (tracts) in the living human brain. The health of these tracts is an important factor underlying many cognitive and neurological disorders. In vivo, tissue properties may vary systematically along each tract for several reasons: different populations of axons enter and exit the tract, and disease can strike at local positions within the tract. Hence quantifying and understanding diffusion measures along each fiber tract (Tract Profile) may reveal new insights into white matter development, function, and disease that are not obvious from mean measures of that tract. We demonstrate several novel findings related to Tract Profiles in the brains of typically developing children and children at risk for white matter injury secondary to preterm birth. First, fractional anisotropy (FA) values vary substantially within a tract but the Tract FA Profile is consistent across subjects. Thus, Tract Profiles contain far more information than mean diffusion measures. Second, developmental changes in FA occur at specific positions within the Tract Profile, rather than along the entire tract. Third, Tract Profiles can be used to compare white matter properties of individual patients to standardized Tract Profiles of a healthy population to elucidate unique features of that patient's clinical condition. Fourth, Tract Profiles can be used to evaluate the association between white matter properties and behavioral outcomes. Specifically, in the preterm group reading ability is positively correlated with FA measured at specific locations on the left arcuate and left superior longitudinal fasciculus and the magnitude of the correlation varies significantly along the Tract Profiles. We introduce open source software for automated fiber-tract quantification (AFQ) that measures Tract Profiles of MRI parameters for 18 white matter tracts. With further validation, AFQ Tract Profiles have potential for informing clinical management and decision-making.
PLoS ONE 01/2012; 7(11):e49790. · 4.09 Impact Factor
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ABSTRACT: A century of neurology and neuroscience shows that seeing words depends on ventral occipital-temporal (VOT) circuitry. Typically, reading is learned using high-contrast line-contour words. We explored whether a specific VOT region, the visual word form area (VWFA), learns to see only these words or recognizes words independent of the specific shape-defining visual features. Word forms were created using atypical features (motion-dots, luminance-dots) whose statistical properties control word-visibility. We measured fMRI responses as word form visibility varied, and we used TMS to interfere with neural processing in specific cortical circuits, while subjects performed a lexical decision task. For all features, VWFA responses increased with word-visibility and correlated with performance. TMS applied to motion-specialized area hMT+ disrupted reading performance for motion-dots, but not line-contours or luminance-dots. A quantitative model describes feature-convergence in the VWFA and relates VWFA responses to behavioral performance. These findings suggest how visual feature-tolerance in the reading network arises through signal convergence from feature-specialized cortical areas.
Neuron 09/2011; 71(5):941-53. · 14.74 Impact Factor
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ABSTRACT: For more than a century, neurologists have hypothesized that the arcuate fasciculus carries signals that are essential for language function; however, the relevance of the pathway for particular behaviors is highly controversial. The primary objective of this study was to use diffusion tensor imaging to examine the relationship between individual variation in the microstructural properties of arcuate fibers and behavioral measures of language and reading skills. A second objective was to use novel fiber-tracking methods to reassess estimates of arcuate lateralization. In a sample of 55 children, we found that measurements of diffusivity in the left arcuate correlate with phonological awareness skills and arcuate volume lateralization correlates with phonological memory and reading skills. Contrary to previous investigations that report the absence of the right arcuate in some subjects, we demonstrate that new techniques can identify the pathway in every individual. Our results provide empirical support for the role of the arcuate fasciculus in the development of reading skills.
Journal of Cognitive Neuroscience 05/2011; 23(11):3304-17. · 5.18 Impact Factor
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ABSTRACT: In this article, cross-relaxation imaging is applied to human ex vivo knee cartilage, and correlations of the cross-relaxation imaging parameters with macromolecular content in articular cartilage are reported. We show that, unlike the more commonly used magnetization transfer ratio, the bound pool fraction, the cross-relaxation rate (k) and the longitudinal relaxation time (T(1)) vary with depth and can therefore provide insight into the differences between the top and bottom layers of articular cartilage. Our cross-relaxation imaging model is more sensitive to macromolecular content in the top layers of cartilage, with bound pool fraction showing moderate correlations with proteoglycan content, and k and T(1) exhibiting moderate correlations with collagen.
Magnetic Resonance in Medicine 03/2011; 66(3):725-34. · 2.96 Impact Factor
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Mohammad Dastjerdi,
Brett L Foster,
Sharmin Nasrullah,
Andreas M Rauschecker, Robert F Dougherty,
Jennifer D Townsend,
Catie Chang,
Michael D Greicius,
Vinod Menon,
Daniel P Kennedy,
Josef Parvizi
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ABSTRACT: The electrophysiological basis for higher brain activity during rest and internally directed cognition within the human default mode network (DMN) remains largely unknown. Here we use intracranial recordings in the human posteromedial cortex (PMC), a core node within the DMN, during conditions of cued rest, autobiographical judgments, and arithmetic processing. We found a heterogeneous profile of PMC responses in functional, spatial, and temporal domains. Although the majority of PMC sites showed increased broad gamma band activity (30-180 Hz) during rest, some PMC sites, proximal to the retrosplenial cortex, responded selectively to autobiographical stimuli. However, no site responded to both conditions, even though they were located within the boundaries of the DMN identified with resting-state functional imaging and similarly deactivated during arithmetic processing. These findings, which provide electrophysiological evidence for heterogeneity within the core of the DMN, will have important implications for neuroimaging studies of the DMN.
Proceedings of the National Academy of Sciences 02/2011; 108(7):3023-8. · 9.68 Impact Factor
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ABSTRACT: Diffusion imaging and bound pool fraction (BPF) mapping are two quantitative magnetic resonance imaging techniques that measure microstructural features of the white matter of the brain. Diffusion imaging provides a quantitative measure of the diffusivity of water in tissue. BPF mapping is a quantitative magnetization transfer (qMT) technique that estimates the proportion of exchanging protons bound to macromolecules, such as those found in myelin, and is thus a more direct measure of myelin content than diffusion. In this work, we combined BPF estimates of macromolecular content with measurements of diffusivity within human white matter tracts. Within the white matter, the correlation between BPFs and diffusivity measures such as fractional anisotropy and radial diffusivity was modest, suggesting that diffusion tensor imaging and bound pool fractions are complementary techniques. We found that several major tracts have high BPF, suggesting a higher density of myelin in these tracts. We interpret these results in the context of a quantitative tissue model.
NeuroImage 01/2011; 54(2):1112-21. · 5.89 Impact Factor
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ABSTRACT: The ability to extract visual word forms quickly and efficiently is essential for using reading as a tool for learning. We describe the first longitudinal fMRI study to chart individual changes in cortical sensitivity to written words as reading develops. We conducted four annual measurements of brain function and reading skills in a heterogeneous group of children, initially 7-12 years old. The results show age-related increase in children's cortical sensitivity to word visibility in posterior left occipito-temporal sulcus (LOTS), nearby the anatomical location of the visual word form area. Moreover, the rate of increase in LOTS word sensitivity specifically correlates with the rate of improvement in sight word efficiency, a measure of speeded overt word reading. Other cortical regions, including V1, posterior parietal cortex, and the right homologue of LOTS, did not demonstrate such developmental changes. These results provide developmental support for the hypothesis that LOTS is part of the cortical circuitry that extracts visual word forms quickly and efficiently and highlight the importance of developing cortical sensitivity to word visibility in reading acquisition.
Journal of Cognitive Neuroscience 01/2011; 23(9):2387-99. · 5.18 Impact Factor
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Moriah E Thomason, Robert F Dougherty,
Natalie L Colich,
Lee M Perry,
Elena I Rykhlevskaia,
Hugo M Louro,
Joachim F Hallmayer,
Christian E Waugh,
Roland Bammer,
Gary H Glover,
Ian H Gotlib
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ABSTRACT: Diffusion tensor imaging is widely used to evaluate the development of white matter. Information about how alterations in major neurotransmitter systems, such as the dopamine (DA) system, influence this development in healthy children, however, is lacking. Catechol-O-metyltransferase (COMT) is the major enzyme responsible for DA degradation in prefrontal brain structures, for which there is a corresponding genetic polymorphism (val158met) that confers either a more or less efficient version of this enzyme. The result of this common genetic variation is that children may have more or less available synaptic DA in prefrontal brain regions. In the present study we examined the relation between diffusion properties of frontal white matter structures and the COMT val158met polymorphism in 40 children ages 9-15. We found that the val allele was associated with significantly elevated fractional anisotropy values and reduced axial and radial diffusivities. These results indicate that the development of white matter in healthy children is related to COMT genotype and that alterations in white matter may be related to the differential availability of prefrontal DA. This investigation paves the way for further studies of how common functional variants in the genome might influence the development of brain white matter.
NeuroImage 11/2010; 53(3):926-34. · 5.89 Impact Factor
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ABSTRACT: Abnormal visual input during development has dramatic effects on the visual system. How does the adult visual system respond when input is corrected? MM lost his left eye and became blind in the right due to corneal damage at the age of 3. At age 46, MM regained his retinal image, but his visual abilities, even seven years following the surgery, remain severely limited, and he does not rely on vision for daily life. Neuroimaging measurements reveal several differences among MM, sighted controls, sighted monocular, and early blind subjects. We speculate that these differences stem from damage during the critical period in development of retinal neurons with small, foveal receptive fields. In this case, restoration of functional vision requires more than improving retinal image contrast. In general, visual restoration will require accounting for the developmental trajectory of the individual and the consequences of the early deprivation on cortical circuitry.
Neuron 01/2010; 65(1):21-31. · 14.74 Impact Factor
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ABSTRACT: Functional MRI studies of mental arithmetic consistently report blood oxygen level-dependent signals in the parietal and frontal regions. We tested whether white matter pathways connecting these regions are related to mental arithmetic ability by using diffusion tensor imaging (DTI) to measure these pathways in 28 children (age 10-15 years, 14 girls) and assessing their mental arithmetic skills. For each child, we identified anatomically the anterior portion of the superior longitudinal fasciculus (aSLF), a pathway connecting parietal and frontal cortex. We measured fractional anisotropy in a core region centered along the length of the aSLF. Fractional anisotropy in the left aSLF positively correlates with arithmetic approximation skill, as measured by a mental addition task with approximate answer choices. The correlation is stable in adjacent core aSLF regions but lower toward the pathway endpoints. The correlation is not explained by shared variance with other cognitive abilities and did not pass significance in the right aSLF. These measurements used DTI, a structural method, to test a specific functional model of mental arithmetic.
Proceedings of the National Academy of Sciences 11/2009; 106(52):22546-51. · 9.68 Impact Factor
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ABSTRACT: Estimating the complete set of white matter fascicles (the projectome) from diffusion data requires evaluating an enormous number of potential pathways; consequently, most algorithms use computationally efficient greedy methods to search for pathways. The limitation of this approach is that critical global parameters--such as data prediction error and white matter volume conservation--are not taken into account. We describe BlueMatter, a parallel algorithm for global projectome evaluation, which uniquely accounts for global prediction error and volume conservation. Leveraging the BlueGene/L supercomputing architecture, BlueMatter explores a massive database of 180 billion candidate fascicles. The candidates are derived from several sources, including atlases and multiple tractography algorithms. Using BlueMatter we created the highest resolution, volume-conserved projectome of the human brain.
Medical image computing and computer-assisted intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention. 01/2009; 12(Pt 1):861-8.
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ABSTRACT: We describe the case of a child ("S") who was treated with radiation therapy at age 5 for a recurrent malignant brain tumor. Radiation successfully abolished the tumor but caused radiation-induced tissue necrosis, primarily affecting cerebral white matter. S was introduced to us at age 15 because of her profound dyslexia. We assessed cognitive abilities and performed diffusion tensor imaging (DTI) to measure cerebral white matter pathways. Diffuse white matter differences were evident in T1-weighted, T2-weighted, diffusion anisotropy, and mean diffusivity measures in S compared to a group of 28 normal female controls. In addition, we found specific white matter pathway deficits by comparing tensor-orientation directions in S's brain with those of the control brains. While her principal diffusion direction maps appeared consistent with those of controls over most of the brain, there were tensor-orientation abnormalities in the fiber tracts that form the superior longitudinal fasciculus (SLF) in both hemispheres. Tractography analysis indicated that the left and right arcuate fasciculus (AF), as well as other tracts within the SLF, were missing in S. Other major white matter tracts, such as the corticospinal and inferior occipitofrontal pathways, were intact. Functional MRI measurements indicated left-hemisphere dominance for language with a normal activation pattern. Despite the left AF abnormality, S had preserved oral language with average sentence repetition skills. In addition to profound dyslexia, S exhibited visuospatial, calculation, and rapid naming deficits and was impaired in both auditory and spatial working memory. We propose that the reading and visuospatial deficits were due to the abnormal left and right SLF pathways, respectively. These results advance our understanding of the functional significance of the SLF and are the first to link radiation necrosis with selective damage to a specific set of fiber tracts.
Neuropsychologia 09/2008; 47(1):180-94. · 3.64 Impact Factor
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ABSTRACT: Current strategies for thresholding statistical parametric maps in neuroimaging include control of the family-wise error rate, control of the false discovery rate (FDR) and thresholding of the posterior probability of a voxel being active given the data, the latter derived from a mixture model of active and inactive voxels. Correct inference using any of these criteria depends crucially on the specification of the null distribution of the test statistics. In this article we show examples from fMRI and DTI data where the theoretical null distribution does not match well the observed distribution of the test statistics. As a solution, we introduce the use of an empirical null, a null distribution empirically estimated from the data itself, allowing for global corrections of theoretical null assumptions. The theoretical null distributions considered are normal, t, chi(2) and F, all commonly encountered in neuroimaging. The empirical null estimate is accompanied by an estimate of the proportion of non-active voxels in the data. Based on the two-class mixture model, we present the equivalence between the strategies of controlling FDR and thresholding posterior probabilities in the context of neuroimaging and show that the FDR estimates derived from the empirical null can be seen as empirical Bayes estimates.
NeuroImage 05/2008; 44(1):71-82. · 5.89 Impact Factor
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ABSTRACT: Diffusion tensor imaging (DTI) is a novel modality of magnetic resonance imaging that allows noninvasive mapping of the brain's white matter. A particular map derived from DTI measurements is a map of water principal diffusion directions, which are proxies for neural fiber directions. We consider a study in which diffusion direction maps were acquired for two groups of subjects. The objective of the analysis is to find regions of the brain in which the corresponding diffusion directions differ between the groups. This is attained by first computing a test statistic for the difference in direction at every brain location using a Watson model for directional data. Interesting locations are subsequently selected with control of the false discovery rate. More accurate modeling of the null distribution is obtained using an empirical null density based on the empirical distribution of the test statistics across the brain. Further, substantial improvements in power are achieved by local spatial averaging of the test statistic map. Although the focus is on one particular study and imaging technology, the proposed inference methods can be applied to other large scale simultaneous hypothesis testing problems with a continuous underlying spatial structure.
04/2008;
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ABSTRACT: Magnetic resonance diffusion-weighted imaging coupled with fiber tractography (DFT) is the only non-invasive method for measuring white matter pathways in the living human brain. DFT is often used to discover new pathways. But there are also many applications, particularly in visual neuroscience, in which we are confident that two brain regions are connected, and we wish to find the most likely pathway forming the connection. In several cases, current DFT algorithms fail to find these candidate pathways. To overcome this limitation, we have developed a probabilistic DFT algorithm (ConTrack) that identifies the most likely pathways between two regions. We introduce the algorithm in three parts: a sampler to generate a large set of potential pathways, a scoring algorithm that measures the likelihood of a pathway, and an inferential step to identify the most likely pathways connecting two regions. In a series of experiments using human data, we show that ConTrack estimates known pathways at positions that are consistent with those found using a high quality deterministic algorithm. Further we show that separating sampling and scoring enables ConTrack to identify valid pathways, known to exist, that are missed by other deterministic and probabilistic DFT algorithms.
Journal of Vision 02/2008; 8(9):15.1-16. · 3.38 Impact Factor
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ABSTRACT: Measuring the properties of the white matter pathways from retina to cortex in the living human brain will have many uses for understanding visual performance and guiding clinical treatment. For example, identifying the Meyer's loop portion of the optic radiation (OR) has clinical significance because of the large number of temporal lobe resections. We use diffusion tensor imaging and fiber tractography (DTI-FT) to identify the most likely pathway between the lateral geniculate nucleus (LGN) and the calcarine sulcus in sixteen hemispheres of eight healthy volunteers. Quantitative population comparisons between DTI-FT estimates and published postmortem dissections match with a spatial precision of about 1 mm. The OR can be divided into three bundles that are segmented based on the direction of the fibers as they leave the LGN: Meyer's loop, central, and direct. The longitudinal and radial diffusivities of the three bundles do not differ within the measurement noise; there is a small difference in the radial diffusivity between the right and left hemispheres. We find that the anterior tip of Meyer's loop is 28 +/- 3 mm posterior to the temporal pole, and the population range is 1 cm. Hence, it is important to identify the location of this bundle in individual subjects or patients.
Journal of Vision 02/2008; 8(10):12.1-11. · 3.38 Impact Factor
