Biomedical subjects

Darren R Gitelman

Publications and source records attributed to Darren R Gitelman.

12 recordsLinked to original sources

PubMed2003

Primary progressive aphasia: PPA and the language network.

Primary Progressive Aphasia (PPA) is a behaviorally focal dementia syndrome with deterioration of language functions but relative preservation of other cognitive domains for at least the first two years of disease. In this study, PPA patients with impaired word finding but intact comprehension of conversational speech and their matched control subjects were examined using voxel-based morphometry (VBM) and functional magnetic resonance imaging (fMRI). fMRI compared signal changes during phonological and semantic language tasks with those during a control task (matching letters). PPA patients showed longer reaction times and reduced accuracy versus controls on the language tasks, but no performance differences on the control task. VBM demonstrated reduced gray matter in left superior temporal and inferior parietal regions in the PPA group. However, these patients showed a normal pattern of activation within the classical language regions. In addition, PPA patients showed activations, not seen in normals, in fusiform gyrus, precentral gyrus, and intra-parietal sulcus. These activations were found to correlate negatively with measures of naming and task performance. The additional activations in PPA may therefore represent a compensatory spread of language-related neural activity or a failure to suppress activity in areas normally inhibited during language tasks.

Aged↗

PubMed2003

Cerebral hemispheric specialization for spatial attention: spatial distribution of search-related eye fixations in the absence of neglect.

The "specialization" of the right hemisphere for spatial attention is widely accepted but poorly understood. While several theories have been supported by studies of patients with acute hemispatial neglect, generalizability beyond this population remains unclear. In this study, we compared the predictions of two attention models [Brain 119 (1996) 841; Trans. Am. Neurol. Assoc. 95 (1970) 143] when applied to data obtained from subjects with unilateral right- or left-cerebral lesions, but without clinical evidence of neglect during a visual search task. Both Left Lesion and Right Lesion subjects detected fewer targets in the contralesional hemispace. However, the Right Lesion subjects also made fewer visual fixations and longer saccades in the contralesional hemispace, suggesting a fundamental alteration in the architecture of visual search. The spatial distribution of fixations made by Right Lesion subjects more closely fits the prediction of a "salience" model than of the strict interpretation of a linear "gradient" model. These data support the long-standing notion of right hemisphere dominance for spatial attention, especially for the top-down processes entailed in self-directed visual search, and extend this to lesion patients without clinically evident neglect. A theoretical model based on the salience of extrapersonal space appears useful for understanding alterations of attentional allocation, particularly after recovery from stroke.

Adult↗

PubMed2003

Attention and its disorders.

This chapter focuses on the clinical aspects of attention including anatomy, cognitive neuropsychology, disorders, and functional imaging evidence for the role of attention in cognition. Particular emphasis is given to selected aspects of visual attention. Imaging studies discussed are primarily functional magnetic resonance imaging (fMRI) and positron emission tomography (PET). In addition, some evidence will be provided from the time-honoured clinical method of lesion studies.

Attention↗

PubMed2002

Neural correlates of successful encoding identified using functional magnetic resonance imaging.

Neural activity that occurs during the creation of a new memory trace can be observed using functional magnetic resonance imaging (fMRI). Event-related designs have been used to demonstrate that activity in prefrontal and medial temporal lobe areas is associated with successful memory storage. Here we contrasted activity associated with encoding success and encoding effort. Participants viewed a series of 150 words but attempted to remember only half of them. Encoding effort was manipulated using a cue in the form of a letter (R or F) presented after each word to instruct participants either to remember or to forget that word. Increased activity in left inferior prefrontal cortex was observed when words were followed by the cue to remember. In contrast, increased left medial temporal lobe activity was observed for words that were successfully recalled later. These results show that fMRI correlates of the intention to encode a word are different from fMRI correlates of whether that encoding is successful. Prefrontal activation was strongly associated with intentional verbal encoding, whereas left medial temporal activation was crucial for the encoding that actually led to successful memory on the subsequent test.

Adolescent↗

PubMed2002

Functional changes in temporal lobe activity during transient global amnesia.

The integrity of temporal lobe activity during and after recovery from transient global amnesia (TGA) was assessed in a case study using functional MRI. TGA was associated with scene-encoding deficits in a temporolimbic circuit that recovered over time. Frontoparietal areas recruited during the amnesic state may signify a compensatory reliance on visuospatial or working memory strategies. Reduction of extrastriate cortex responses over repeated testing sessions possibly indicates intact visual priming in TGA.

Adult↗

PubMed2002

Modality independence of word comprehension.

Functional magnetic resonance imaging (fMRI) was used to examine the functional anatomy of word comprehension in the auditory and visual modalities of presentation. We asked our subjects to determine if word pairs were semantically associated (e.g., table, chair) and compared this to a reference task where they were asked to judge whether word pairs rhymed (e.g., bank, tank). This comparison showed task-specific and modality-independent activation for semantic processing in the heteromodal cortices of the left inferior frontal gyrus (BA 46, 47) and left middle temporal gyrus (BA 21). There were also modality-specific activations in the fusiform gyrus (BA 37) for written words and in the superior temporal gyrus (BA 22) for spoken words. Our findings are consistent with the hypothesis that word form recognition (lexical encoding) occurs in unimodal cortices and that heteromodal brain regions in the anterior as well as posterior components of the language network subserve word comprehension (semantic decoding).

Adult↗

PubMed2002

On the use of caffeine as a contrast booster for BOLD fMRI studies.

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.

Adult↗

PubMed2002

Functional anatomy of visual search: regional segregations within the frontal eye fields and effective connectivity of the superior colliculus.

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.

Adult↗

PubMed2002

Functional anatomy of intra- and cross-modal lexical tasks.

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.

Adult↗

PubMed2002

Effective connectivity and intersubject variability: using a multisubject network to test differences and commonalities.

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 x 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.

Adult↗

PubMed2002

ILAB: a program for postexperimental eye movement analysis.

The recording and analysis of eye movements are fundamental to a diverse set of research applications, including studies in which reading, visual search, and both overt and covert visuospatial attention are examined. Software tools supplied with commonly available eye-tracking equipment have generally been limited in functionality and nonextensible. Because of this dearth of available software, ELAB was created to provide an extensible framework for analyzing various aspects of eye movements. The program consists of a series of open-source MATLAB functions. The program's data structures keep raw data, analysis preferences, and analyzed data separate, thus maintaining data fidelity and promoting extensibility.

Blinking↗

PubMed2002

Hemodynamic response changes in cerebrovascular disease: implications for functional MR imaging.

BACKGROUND AND PURPOSE: Patients with cerebrovascular occlusive disease may develop compensatory changes in local cerebral vasculature with a resultant loss of vascular reactivity. These alterations can affect the blood oxygen level-dependent (BOLD) signal that is the basis for functional MR imaging. We investigated the BOLD signal in patients with unilateral cerebrovascular disease to ascertain the clinical utility of functional MR imaging in these patients. METHODS: Five healthy volunteers and three patients with cerebro-occlusive disease were imaged with both a block and an event-related design of a visually cued bilateral motor task. Activation maps were calculated, and individual hemodynamic response curves were generated for left and right primary motor cortices. Vascular reserve was determined for the relevant vascular territory by using transcranial Doppler ultrasonography (US). RESULTS: In the event-related data, the amplitude of the BOLD response was significantly decreased in the motor cortex ipsilateral to the stenosis and showed significant delays in the timing of the hemodynamic response. In contrast, the longer duration stimulus and longer TR of the block design showed significant decreases in the BOLD amplitude but no significant interhemispheric temporal differences. Corroborating the hemodynamic status, transcranial Doppler US analysis showed diminished vascular reserve ipsilateral to the lesion. CONCLUSION: Differences in the results between the event-related and block paradigms reflect the sensitivity to alterations in autoregulation or vascular compliance. These changes in the vasculature directly affect the BOLD contrast underlying functional MR imaging. Thus, while this technique remains a useful clinical tool, caution is warranted when studying patients with cerebrovascular disease.

Adult↗