Arrow Research search

Author name cluster

Darren R. Gitelman

Possible papers associated with this exact author name in Arrow. This page groups case-insensitive exact name matches and is not a full identity disambiguation profile.

22 papers
1 author row

Possible papers

22

YNIMG Journal 2023 Journal Article

Optimizing quantification of MK6240 tau PET in unimpaired older adults

  • Theresa M. Harrison
  • Tyler J. Ward
  • Alice Murphy
  • Suzanne L. Baker
  • Pablo A. Dominguez
  • Robert Koeppe
  • Prashanthi Vemuri
  • Samuel N. Lockhart

F]florbetaben [FBB]) and MRI data to evaluate neuroimaging biomarkers of AD and cerebrovascular pathophysiology in this at-risk sample. Here 481 participants (70.0±5.0; 66% F) with baseline MK6240, FBB and structural MRI scans were included. PET scans were coregistered to the structural MRI which was used to create FreeSurfer-defined reference regions and target regions of interest (ROIs). We also created off-target signal (OTS) ROIs to examine the magnitude and distribution of MK6240 OTS across the brain as well as relationships between OTS and age, sex, and race. OTS was unimodally distributed, highly correlated across OTS ROIs and related to younger age and sex but not race. Aiming to identify an optimal processing approach for MK6240 that would reduce the influence of OTS, we compared our previously validated MRI-guided standard PET processing and 6 alternative approaches. The alternate approaches included combinations of reference region erosion and meningeal OTS masking before spatial smoothing as well as partial volume correction. To compare processing approaches we examined relationships between target ROIs (entorhinal cortex (ERC), hippocampus or a temporal meta-ROI (MetaROI)) SUVR and age, sex, race, Aβ and a general cognitive status measure, the Modified Telephone Interview for Cognitive Status (TICSm). Overall, the processing approaches performed similarly, and none showed a meaningful improvement over standard processing. Across processing approaches we observed previously reported relationships with MK6240 target ROIs including positive associations with age, an Aβ+> Aβ- effect and negative associations with cognition. In sum, we demonstrated that different methods for minimizing effects of OTS, which is highly correlated across the brain within subject, produced no substantive change in our performance metrics. This is likely because OTS contaminates both reference and target regions and this contamination largely cancels out in SUVR data. Caution should be used when efforts to reduce OTS focus on target or reference regions in isolation as this may exacerbate OTS contamination in SUVR data.

Details DOI

YNIMG Journal 2007 Journal Article

Developmental changes in activation and effective connectivity in phonological processing

  • Tali Bitan
  • Jimmy Cheon
  • Dong Lu
  • Douglas D. Burman
  • Darren R. Gitelman
  • M-Marsel Mesulam
  • James R. Booth

The current study examined developmental changes in activation and effective connectivity among brain regions during a phonological processing task, using fMRI. Participants, ages 9–15, were scanned while performing rhyming judgments on pairs of visually presented words. The orthographic and phonological similarity between words in the pair was independently manipulated, so that rhyming judgment could not be based on orthographic similarity. Our results show a developmental increase in activation in the dorsal part of left inferior frontal gyrus (IFG), accompanied by a decrease in the dorsal part of left superior temporal gyrus (STG). The coupling of dorsal IFG with other selected brain regions involved in the phonological decision increased with age, while the coupling of STG decreased with age. These results suggest that during development there is a shift from reliance on sensory auditory representations to reliance on phonological segmentation and covert articulation for performing rhyming judgment on visually presented words. In addition, we found a developmental increase in activation in left posterior parietal cortex that was not accompanied by a change in its connectivity with the other regions. These results suggest that maturational changes within a cortical region are not necessarily accompanied by an increase in its interactions with other regions and its contribution to the task. Our results are consistent with the idea that there is reduced reliance on primary sensory processes as task-relevant processes mature and become more efficient during development.

Details DOI

YNIMG Journal 2006 Journal Article

Weaker top–down modulation from the left inferior frontal gyrus in children

  • Tali Bitan
  • Douglas D. Burman
  • Dong Lu
  • Nadia E. Cone
  • Darren R. Gitelman
  • M-Marsel Mesulam
  • James R. Booth

Previous studies have shown that developmental changes in the structure and function of prefrontal regions can continue throughout childhood and adolescence. Our recent results suggested a role for the left inferior frontal cortex in modulating task-dependent shifts in effective connectivity when adults focus on orthographic versus phonological aspects of presented words. Specifically, the top–down influence of the inferior frontal cortex determined whether incoming word-form information from the fusiform gyrus would have a greater impact on the parietal areas involved in orthographic processing or temporal areas involved in phonological processing (Bitan, T. , Booth, J. R. , Choy, J. , Burman, D. D. , Gitelman, D. R. and Mesulam, M. -M. , 2005. Shifts of Effective Connectivity within a Language Network during Rhyming and Spelling. J. Neurosci. 25, 5397–5403.). In the current study, we find that children displayed an identical pattern of task-dependent functional activations within this network. In comparison to adults, however, children had significantly weaker top–down modulatory influences emanating from the inferior frontal area. Adult language processing may thus involve greater top–down cognitive control compared to children, resulting in less interference from task-irrelevant information.

Details DOI

YNIMG Journal 2005 Journal Article

Language network specializations: An analysis with parallel task designs and functional magnetic resonance imaging

  • Darren R. Gitelman
  • Anna C. Nobre
  • Sreepadma Sonty
  • Todd B. Parrish
  • M-Marsel Mesulam

Although the classical core regions of the language system (Broca's and Wernicke's areas) were defined over a century ago, it took the advent of functional imaging to sharpen our understanding of how these regions and adjacent parts of the brain are associated with particular aspects of language. One limitation of such studies has been the need to compare results across different subject groups, each performing a different type of language task. Thus, this study was designed to examine overlapping versus segregated brain activations associated with three fundamental language tasks, orthography, phonology and semantics performed by the same subjects during a single experimental session. The results demonstrate a set of primarily left-sided core language regions in ventrolateral frontal, supplementary motor, posterior mid-temporal, occipito-temporal and inferior parietal areas, which were activated for all language tasks. Segregated task-specific activations were demonstrated within the ventrolateral frontal, mid-temporal and inferior parietal areas. Within the inferior frontal cortex (Broca's regional complex), segregated activations were seen for the semantic and phonological tasks. These findings demonstrate both common and task specific activations within the language system.

Details DOI

YNIMG Journal 2003 Journal Article

Modeling regional and psychophysiologic interactions in fMRI: the importance of hemodynamic deconvolution

  • Darren R. Gitelman
  • William D. Penny
  • John Ashburner
  • Karl J. Friston

The analysis of functional magnetic resonance imaging (fMRI) time-series data can provide information not only about task-related activity, but also about the connectivity (functional or effective) among regions and the influences of behavioral or physiologic states on that connectivity. Similar analyses have been performed in other imaging modalities, such as positron emission tomography. However, fMRI is unique because the information about the underlying neuronal activity is filtered or convolved with a hemodynamic response function. Previous studies of regional connectivity in fMRI have overlooked this convolution and have assumed that the observed hemodynamic response approximates the neuronal response. In this article, this assumption is revisited using estimates of underlying neuronal activity. These estimates use a parametric empirical Bayes formulation for hemodynamic deconvolution.

Details DOI

YNIMG Journal 2002 Journal Article

Effective Connectivity and Intersubject Variability: Using a Multisubject Network to Test Differences and Commonalities

  • Andrea Mechelli
  • Will D. Penny
  • Cathy J. Price
  • Darren R. Gitelman
  • Karl J. Friston

This article is about intersubject variability in the functional integration of activity in different brain regions. Previous studies of functional and effective connectivity have dealt with intersubject variability by analyzing data from different subjects separately or pretending the data came from the same subject. These approaches do not allow one to test for differences among subjects. The aim of this work was to illustrate how differences in connectivity among subjects can be addressed explicitly using structural equation modeling. This is enabled by constructing a multisubject network that comprises m regions of interest for each of the n subjects studied, resulting in a total of m × n nodes. Constructing a network of regions from different subjects may seem counterintuitive but embodies two key advantages. First, it allows one to test directly for differences among subjects by comparing models that do and do not allow a particular connectivity parameter to vary over subjects. Second, a multisubject network provides additional degrees of freedom to estimate the model's free parameters. Any neurobiological hypothesis normally addressed by single-subject or group analyses can still be tested, but with greater sensitivity. The common influence of experimental variables is modeled by connecting a virtual node, whose time course reflects stimulus onsets, to the sensory or “input” region in all subjects. Further experimental changes in task or cognitive set enter through modulation of the connections. This approach allows one to model both endogenous (or intrinsic) variance and exogenous effects induced by experimental design. We present a functional magnetic resonance imaging study that uses a multisubject network to investigate intersubject variability in functional integration in the context of single word and pseudoword reading. We tested whether the effect of word type on the reading-related coupling differed significantly among subjects. Our results showed that a number of forward and backward connections were stronger for reading pseudowords than words, and, in one case, connectivity showed significant intersubject variability. The discussion focuses on the implications of our findings and on further applications of the multisubject network analysis.

Details DOI

YNIMG Journal 2002 Journal Article

Functional Anatomy of Intra- and Cross-Modal Lexical Tasks

  • James R. Booth
  • Douglas D. Burman
  • Joel R. Meyer
  • Darren R. Gitelman
  • Todd B. Parrish
  • M.Marsel Mesulam

Functional magnetic resonance imaging (fMRI) was used to examine lexical processing in normal adults (20–35 years). Two tasks required only intramodal processing (spelling judgments with visual input and rhyming judgments with auditory input) and two tasks required cross-modal processing between phonologic and orthographic representations (spelling judgments with auditory input and rhyming judgments with visual input). Each task led to greater activation in the unimodal association area concordant with the modality of input, namely fusiform gyrus (BA 19, 37) for written words and superior temporal gyrus (BA 22, 42) for spoken words. Cross-modal tasks generated greater activation in posterior heteromodal regions including the supramarginal and angular gyri (BA 40, 39). Cross-modal tasks generated additional activation in unimodal areas representing the target of conversion, superior temporal gyrus for visual rhyming and fusiform gyrus for auditory spelling. Our findings suggest that the fusiform gyrus processes orthographic word forms, the superior temporal gyrus processes phonologic word forms, and posterior heteromodal regions are involved in the conversion between orthography and phonology.

Details DOI

YNIMG Journal 2002 Journal Article

Functional Anatomy of Visual Search: Regional Segregations within the Frontal Eye Fields and Effective Connectivity of the Superior Colliculus

  • Darren R. Gitelman
  • Todd B. Parrish
  • Karl J. Friston
  • M.-Marsel Mesulam

The ability to find targets embedded within complex visual environments requires the dynamic programming of visuomotor search behaviors. Functional magnetic resonance imaging was used to image subjects while they visually searched for targets embedded among foils. Visuomotor search activated the posterior parietal cortex and the frontal eye fields. Both regions showed a greater number of activated voxels on the right, consistent with the known pattern of right hemispheric dominance for spatial attention. The superior colliculus showed prominent activation in the search versus eye movement contrast, demonstrating, for the first time in humans, activation of this region specifically related to an exploratory attentional contingency. An analysis of effective connectivity demonstrated that the search-dependent variance in the activity of the superior colliculus was significantly influenced by the activity in a network of cortical regions including the right frontal eye fields and bilateral parietal and occipital cortices. These experiments also revealed the presence of a mosaic of activated sites within the frontal eye field region wherein saccadic eye movements, covert shifts of attention, and visuomotor search elicited overlapping but not identical zones of activation. In contrast to the existing literature on functional imaging, which has focused on covert shifts of spatial attention, this study helps to characterize the functional anatomy of overt spatial exploration.

Details DOI

YNIMG Journal 2002 Journal Article

On the Use of Caffeine as a Contrast Booster for BOLD fMRI Studies

  • Todd A. Mulderink
  • Darren R. Gitelman
  • M.-Marsel Mesulam
  • Todd B. Parrish

This study explored the possible use of caffeine as an agent to improve the BOLD (blood oxygen level-dependent) signal response in fMRI. Previous research has demonstrated that caffeine has the ability to reset the level of coupling between blood flow and neuronal activity. In the present study, it has been shown that caffeine causes a decrease in cerebral perfusion by as much as 13. 2% without a change in performance. Caffeine is a cerebral vasoconstrictor that causes an increase in the concentration of deoxyhemoglobin and thus a decrease in the BOLD baseline resting signal by 4. 4%. During activation, the vasculature responds from below-normal baseline levels with a normal increase in blood flow and volume, resulting in an overall increase in the BOLD contrast. This increase can be as large as 22–37% during the performance of a visually cued motor task. The benefit of such a large increase in the BOLD contrast could be used to improve the image resolution, the acquisition scheme, or the task design of fMRI experiments. Caffeine has the potential to be used as a contrast booster for fMRI experiments.

Details DOI

YNIMG Journal 2001 Journal Article

Heterogeneity of Cingulate Contributions to Spatial Attention

  • M.Marsel Mesulam
  • Anna C. Nobre
  • Yun-Hee Kim
  • Todd B. Parrish
  • Darren R. Gitelman

Functional magnetic resonance imaging was used to investigate activation patterns within the cingulate region during tasks based on spatial attention. Subjects were asked to detect targets which appeared either at the site indicated by a cue or on the opposite side. A “cue effect” was identified by the presence of shorter reaction times to validly than invalidly cued targets, showing that an anticipatory bias had been generated in the direction of the cue. Target detection accuracy was consistently above 90% although cue effects and reaction times displayed substantial variations, from one task session to another. Activation within the anterior cingulate region was seen in 16 of the 26 sessions but showed no correlation with reaction time. Posterior cingulate activation was seen in only 6 of the 26 sessions. However, a random effects analysis showed that the task-related signal change in this region was strongly correlated with the speed of target detection. A post hoc analysis indicated that this correlation was significant only when cue effects were present. No other part of the cerebral cortex displayed significant correlations with reaction times or cue effects. These results suggest that the cingulate component of the attentional network has at least two functionally segregated sectors, an anterior one in BA 24/32 and a posterior cingulo-retrosplenial one in BA 23/29/30. The posterior sector appears to be associated with the speed of detecting spatial targets, especially when attention is under the influence of a cue-induced anticipatory bias. The anterior cingulate focus did not display such a relationship in our tasks and is likely to mediate other aspects of attentional deployment such as performance monitoring, response selection or target identification.

Details DOI

YNIMG Journal 2001 Journal Article

Voxel-Based Morphometry of Herpes Simplex Encephalitis

  • Darren R. Gitelman
  • John Ashburner
  • Karl J. Friston
  • Lorraine K. Tyler
  • Cathy J. Price

Voxel-based morphometry (VBM) is a powerful tool for analyzing changes in gray or white matter density of the brain. By using an automated segmentation procedure and standardized parametric statistics it avoids biases inherent in operator-dependent morphological operations (J. Ashburner and K. J. Friston, 2000, NeuroImage 11, 805–821). Since its introduction in 1995, VBM has been used to examine anatomical changes in a variety of diseases associated with neurologic and psychiatric dysfunction. Given the power of this technique for discerning subtle anatomical changes, we wanted to assess its performance on brains with gross structural abnormalities. Such results could have implications regarding the difficulties to be faced when examining other types of distorted brains (e. g. , brains with changes due to degenerative disease). This report describes the use of VBM for examining individual and group changes in gray matter concentration in five patients who had recovered from herpes simplex encephalitis (HSE) compared with age- and sex-matched controls. Because HSE tends to affect a specific set of brain regions we thought that this would (1) provide an opportunity to assess the anatomical face validity of VBM, (2) allow us to assess the problems of this technique when used on distorted brains, and (3) provide an in vivo demonstration of the gray matter changes due to HSE. We found that, despite problems in normalizing and segmenting these severely distorted brains, VBM was able to identify correctly a number of the regional gray matter abnormalities in HSE. The results, while consistent with the well-known histopathology of the disease, also demonstrate potential difficulties with this method.

Details DOI

YNIMG Journal 2000 Journal Article

Real-Time Monitoring of Eye Movements Using Infrared Video-oculography during Functional Magnetic Resonance Imaging of the Frontal Eye Fields

  • Darren R. Gitelman
  • Todd B. Parrish
  • Kevin S. LaBar
  • M.-Marsel Mesulam

Monitoring eye movements is a critical aspect of experimental design for studies of spatial attention and visual perception. However, obtaining online eye-movement recordings has been technologically difficult during functional magnetic resonance (MR) imaging studies. Previous approaches to monitoring eye movements either have distorted the MR images or have shown MR-related interference in the recordings. We report a technique using long-range infrared video-oculography to record eye movements without causing artifacts in the MR images. Analysis of the MR signal from a phantom obtained with the eye-movement equipment turned on or off confirmed the absence of significant additional noise in the MR time series. Eye movements of three subjects were monitored while they performed tasks of covert and overt shifts of spatial attention. Activation of the frontal eye fields during the covert task was seen even when the eye-movement recordings demonstrated no significant difference in saccadic eye movements between the baseline and the active conditions.

Details DOI

YNIMG Journal 1999 Journal Article

Neuroanatomic Overlap of Working Memory and Spatial Attention Networks: A Functional MRI Comparison within Subjects

  • Kevin S. LaBar
  • Darren R. Gitelman
  • Todd B. Parrish
  • M.-Marsel Mesulam

Frontal and posterior parietal activations have been reported in numerous studies of working memory and visuospatial attention. To directly compare the brain regions engaged by these two cognitive functions, the same set of subjects consecutively participated in tasks of working memory and spatial attention while undergoing functional MRI (fMRI). The working memory task required the subject to maintain an on-line representation of foveally displayed letters against a background of distracters. The spatial attention task required the subject to shift visual attention covertly in response to a centrally presented directional cue. The spatial attention task had no working memory requirement, and the working memory task had no covert spatial attention requirement. Subjects' ability to maintain central fixation was confirmed outside the MRI scanner using infrared oculography. According to cognitive conjunction analysis, the set of activations common to both tasks included the intraparietal sulcus, ventral precentral sulcus, supplementary motor area, frontal eye fields, thalamus, cerebellum, left temporal neocortex, and right insula. Double-subtraction analyses yielded additional activations attributable to verbal working memory in premotor cortex, left inferior prefrontal cortex, right inferior parietal lobule, precuneus, and right cerebellum. Additional activations attributable to covert spatial attention included the occipitotemporal junction and extrastriate cortex. The use of two different tasks in the same set of subjects allowed us to provide an unequivocal demonstration that the neural networks subserving spatial attention and working memory intersect at several frontoparietal sites. These findings support the view that major cognitive domains are represented by partially overlapping large-scale neural networks. The presence of this overlap also suggests that spatial attention and working memory share common cognitive features related to the dynamic shifting of attentional resources.

Details DOI

YNIMG Journal 1999 Journal Article

The Large-Scale Neural Network for Spatial Attention Displays Multifunctional Overlap But Differential Asymmetry

  • Yun-Hee Kim
  • Darren R. Gitelman
  • Anna C. Nobre
  • Todd B. Parrish
  • Kevin S. LaBar
  • M.-Marsel Mesulam

Functional magnetic resonance imaging (fMRI) was used to determine the brain regions activated by two types of covert visuospatial attentional shifts: one based on exogenous spatial priming and the other on foveally presented cues which endogenously regulated the direction of spatial expectancy. Activations were seen in the cortical and subcortical components of a previously characterized attentional network, namely, the frontal eye fields, posterior parietal cortex, the cingulate gyrus, the putamen, and the thalamus. Additional activations occurred in the anterior insula, dorsolateral prefrontal cortex, temporo-occipital cortex in the middle and inferior temporal gyri, the supplementary motor area, and the cerebellum. Direct comparisons showed a nearly complete overlap in the location of activations resulting from the two tasks. However, the spatial priming task displayed a more pronounced rightward asymmetry of parietal activation, and a conjunction analysis showed that the area of posterior parietal cortex jointly activated by both tasks was more extensive in the right hemisphere. Furthermore, the posterior parietal and temporo-occipital activations were more pronounced in the task of endogenous attentional shifts. The results show that both exogenous (based on spatial priming) and endogenous (based on expectancy cueing) shifts of attention are subserved by a common network of cortical and subcortical regions. However, the differences between the two tasks, especially in the degree of rightward asymmetry, suggests that the pattern of activation within this network may show variations that reflect the specific attributes of the attentional task.

Details DOI
v2026.09.13