Biomedical subjects

R K Fulbright

Publications and source records attributed to R K Fulbright.

At least 19 recordsLinked to original sources

PubMed2001

The functional neural architecture of components of attention in language-processing tasks.

Using functional magnetic resonance imaging we examined three important dimensions of attentional control (selective attention, divided attention, and executive function) in 25 neurologically normal, right-handed men and women, using tasks involving the perception and processing of printed words, spoken words, or both. In the context of language-processing manipulations: selective attention resulted in increased activation at left hemisphere parietal sites as well as at inferior frontal sites, divided attention resulted in additional increases in activation at these same left hemisphere sites and was also uniquely associated with increased activation of homologous sites in the right hemisphere, and executive function (measured during a complex task requiring sequential decision-making) resulted in increased activation at frontal sites relative to all other conditions. Our findings provide support for the belief that specific functional aspects of attentional control in language processing involve widely distributed but distinctive cortical systems, with mechanisms associated with the control of perceptual selectivity involving primarily parietal and inferior frontal sites and executive function engaging specific sites in frontal cortex.

Adult↗

PubMed2001

Functional magnetic resonance imaging of cocaine craving.

OBJECTIVE: Identification of brain activity associated with craving is important for understanding the neurobiology of addiction. METHOD: Brain activity was measured in cocaine addicts and healthy subjects by functional magnetic resonance imaging (fMRI) while the subjects watched videotapes designed to elicit happy feelings, sad feelings, or the desire to use cocaine. The subjects indicated the onset of drug craving or emotional response, allowing comparison of groups before and after such feelings. RESULTS: Robust activation of the anterior cingulate was evident in patients watching cocaine-cue tapes but not in patients watching happy or sad tapes or in healthy subjects under any condition. Anterior cingulate activation preceded the reported onset of craving and was evident in patients who did not report craving. In contrast, patients showed less activation than healthy subjects during the cocaine-cue tapes in areas of the frontal lobes. After the reported onset of craving, cocaine-dependent subjects showed greater activity than healthy subjects in regions that are more active in healthy subjects when they watch sad tapes than when they watch happy tapes, suggesting a physiologic link between cocaine-cue responses and normal dysphoric states. Dynamic aspects of regional brain activations, but not the location of activations, were abnormal in cocaine-dependent subjects watching sad tapes, suggesting more general affective dysregulation. Patients showed low activation of sensory areas during initial viewing of all videotapes, suggesting generalized alteration in neuroresponsiveness. CONCLUSIONS: Cocaine cues lead to abnormally high cingulate and low frontal lobe activation in cocaine addicts. Addicts also show more general abnormalities in affect-related brain activation.

Adult↗

PubMed2001

Functional MR imaging of regional brain activation associated with the affective experience of pain.

OBJECTIVE: Current models propose that the experience of pain includes both sensory and affective components. Our purpose was to use functional MR imaging to determine areas of the brain engaged by the affective dimension of pain. SUBJECTS AND METHODS: Twelve healthy adults underwent functional MR imaging using a gradient-echo echoplanar technique while a cold pressor test, consisting of cold and pain tasks, was applied first to one foot and then to the other. The cold task involved the application of cold water (14-20 degrees C) that was not at a painful level. For the pain task, the water temperature was then lowered to a painful temperature (8-14 degrees C) and subsequently to the pain threshold (3-8 degrees C). Images acquired at room temperature before the cold and pain tasks served as a baseline task. Composite maps of brain activation were generated by comparing the baseline task with the cold task and the cold task with the pain task. The significance of signal changes was estimated by randomization of individual activation maps. RESULTS: Cold-related activation (p < 0.01) was found in the postcentral gyrus bilaterally, laterally, and inferiorly to the primary motor-sensory area of the foot and at a site near the second somatosensory site. Activation also occurred in the frontal lobe (the bilateral middle frontal gyri and the right inferior frontal gyrus), the left anterior insula, the left thalamus, and the superior aspect of the anterior cingulate gyrus (seen at one slice location). Pain-related activation (p < 0.01) included the anterior cingulate gyrus (seen at four slice locations); the superior frontal gyrus, especially on the right; and the right cuneus. CONCLUSION: Compared with the basic sensory processing of pain, the affective dimension of pain activates a cortical network that includes the right superior frontal gyrus, the right cuneus, and a large area of the anterior cingulate gyrus.

Adult↗

PubMed2000

Network analysis of brain activations in working memory: behavior and age relationships.

Forty-six middle-aged female subjects were scanned using functional Magnetic Resonance Imaging (fMRI) during performance of three distinct stages of a working memory task-encoding, rehearsal, and recognition-for both printed pseudowords and visual forms. An expanse of areas, involving the inferior frontal, parietal, and extrastriate cortex, was active in response to stimuli during both the encoding and recognition periods. Additional increases during memory recognition were seen in right prefrontal regions, replicating a now-common finding [for reviews, see Fletcher et al. (1997) Trends Neurosci 20:213-218; MacLeod et al. (1998) NeuroImage 7:41-48], and broadly supporting the Hemispheric Encoding/Retrieval Asymmetry hypothesis [Tulving et al. (1994) Proc Natl Acad Sci USA 91:2016-2020]. Notably, this asymmetry was not qualified by the type of material being processed. A few sites demonstrated higher activity levels during the rehearsal period, in the absence of any new stimuli, including the medial extrastriate, precuneus, and the medial temporal lobe. Further analyses examined relationships among subjects' brain activations, age, and behavioral scores on working memory tests, acquired outside the scanner. Correlations between brain scores and behavior scores indicated that activations in a number of areas, mainly frontal, were associated with performance. A multivariate analysis, Partial Least Squares [McIntosh et al. (1996) NeuroImage 3:143-157, (1997) Hum Brain Map 5:323-327], was then used to extract component effects from this large set of univariate correlations. Results indicated that better memory performance outside the scanner was associated with higher activity at specific sites within the frontal and, additionally, the medial temporal lobes. Analysis of age effects revealed that younger subjects tended to activate more than older subjects in areas of extrastriate cortex, medial frontal cortex, and the right medial temporal lobe; older subjects tended to activate more than younger subjects in the insular cortex, right inferior temporal lobe, and right inferior frontal gyrus. These results extend recent reports indicating that these regions are specifically involved in the memory impairments seen with aging.

Adult↗

PubMed2000

Abnormal ventral temporal cortical activity during face discrimination among individuals with autism and Asperger syndrome.

BACKGROUND: Recognition of individual faces is an integral part of both interpersonal interactions and successful functioning within a social group. Therefore, it is of considerable interest that individuals with autism and related conditions have selective deficits in face recognition (sparing nonface object recognition). METHOD: We used functional magnetic resonance imaging (fMRI) to study face and subordinate-level object perception in 14 high-functioning individuals with autism or Asperger syndrome (the autism group), in comparison with 2 groups of matched normal controls (normal control group ] [NC1] and normal control group 2 [NC2]) (n = 14 for each). Regions of interest (ROIs) were defined in NC1 and then applied in comparisons between NC2 and the autism group. Regions of interest were also defined in NC2 and then applied to comparisons between NC1 and the autism group as a replication study. RESULTS: In the first set of comparisons, we found significant task x group interactions for the size of activation in the right fusiform gyrus (FG) and right inferior temporal gyri (ITG). Post hoc analyses showed that during face (but not object) discrimination, the autism group had significantly greater activation than controls in the right ITG and less activation of the right FG. The replication study showed again that the autism group used the ITG significantly more for processing faces than the control groups, but for these analyses, the effect was now on the left side. Greater ITG activation was the pattern found in both control groups during object processing. CONCLUSIONS: Individuals with autism spectrum disorders demonstrate a pattern of brain activity during face discrimination that is consistent with feature-based strategies that are more typical of nonface object perception.

Adult↗

PubMed2000

Contribution of the anteromedial temporal lobes to the evaluation of facial emotion.

Amygdala damage can result in impairments in evaluating facial expressions largely specific to fear. In contrast, right-hemisphere cortical lesions result in a more global deficit in facial emotion evaluation. This study addressed these 2 contrasting findings by investigating amygdala and adjacent cortical contributions to the evaluation of facial emotion in 12 patients with right and 11 patients with left unilateral anteromedial temporal lobectomy (RTL and LTL, respectively) and 23 normal controls. RTL but not LTL patients revealed impaired intensity ratings that included but were not exclusive to fear, with the most severe deficits confined to expressions related to affective states of withdrawal-avoidance. This suggests that affective hemispheric specializations in cortical function may extend to subcortical limbic regions. In addition, the right amygdala and adjacent cortex may be part of a neural circuit representing facial expressions of withdrawal.

Adult↗

PubMed2000

The angular gyrus in developmental dyslexia: task-specific differences in functional connectivity within posterior cortex.

Converging evidence from neuroimaging studies of developmental dyslexia reveals dysfunction at posterior brain regions centered in and around the angular gyrus in the left hemisphere. We examined functional connectivity (covariance) between the angular gyrus and related occipital and temporal lobe sites, across a series of print tasks that systematically varied demands on phonological assembly. Results indicate that for dyslexic readers a disruption in functional connectivity in the language-dominant left hemisphere is confined to those tasks that make explicit demands on assembly. In contrast, on print tasks that do not require phonological assembly, functional connectivity is strong for both dyslexic and nonimpaired readers. The findings support the view that neurobiological anomalies in developmental dyslexia are largely confined to the phonological-processing domain. In addition, the findings suggest that right-hemisphere posterior regions serve a compensatory role in mediating phonological performance in dyslexic readers.

Adolescent↗

PubMed2000

Cerebrospinal fluid cleft with cortical dimple: MR imaging marker for focal cortical dysgenesis.

PURPOSE: To determine whether the magnetic resonance (MR) imaging feature of a cerebrospinal fluid (CSF) cleft and cortical dimple can be used as a marker for cortical dysgenesis. MATERIALS AND METHODS: MR images in 875 patients with epilepsy were evaluated for the following features of focal cortical dysgenesis: cortical thickening, indistinct junction between gray and white matter, macrogyria, and abnormal sulcal pattern. Images with these features were reevaluated to determine the relationship between the CSF cleft-cortical dimple complex and focal cortical dysgenesis and its contribution to diagnosis. The cleft-dimple complex was defined as a prominent CSF space associated with a region of cortical volume loss adjacent to the dysgenesis. RESULTS: Seventy-one patients had cortical dysgenesis, including 27 with cellular proliferation abnormalities, 18 with migration abnormalities, 25 with cortical organization abnormalities, and one with miscellaneous anomalies. Histologic correlation was available in 20 patients. There was an associated cortical dimple in 29 (41%) patients. This association was strongest in patients with cortical organization abnormalities: It was present in 22 of the 25 (88%) patients. In 12 (48%) patients with abnormalities of cortical organization, the CSF cleft was easier to detect than other features of cortical dysgenesis or contributed directly to the MR imaging diagnosis. CONCLUSION: The cleft-dimple complex is a marker for subtle cases of focal cortical dysgenesis and may be due to maldevelopment. In patients with seizures, the presence of a cleft-dimple complex should alert the physician to scrutinize adjacent regions for developmental anomalies.

Adult↗

PubMed2000

An event-related neuroimaging study distinguishing form and content in sentence processing.

Two coordinated experiments using functional Magnetic Resonance Imaging (fMRI) investigated whether the brain represents language form (grammatical structure) separately from its meaning content (semantics). While in the scanner, 14 young, unimpaired adults listened to simple sentences that were either nonanomalous or contained a grammatical error (for example, *Trees can grew.), or a semantic anomaly (for example, *Trees can eat.). A same&frasl;different tone pitch judgment task provided a baseline that isolated brain activity associated with linguistic processing from background activity generated by attention to the task and analysis of the auditory input. Sites selectively activated by sentence processing were found in both hemispheres in inferior frontal, middle, and superior frontal, superior temporal, and temporo-parietal regions. Effects of syntactic and semantic anomalies were differentiated by some nonoverlapping areas of activation: Syntactic anomaly triggered significantly increased activity in and around Broca's area, whereas semantic anomaly activated several other sites anteriorly and posteriorly, among them Wernicke's area. These dissociations occurred when listeners were not required to attend to the anomaly. The results confirm that linguistic operations in sentence processing can be isolated from nonlinguistic operations and support the hypothesis of a specialization for syntactic processing.

Adult↗

PubMed2000

Preliminary evidence of improved verbal working memory performance and normalization of task-related frontal lobe activation in schizophrenia following cognitive exercises.

OBJECTIVE: The authors' goal was to evaluate the possibility of treating brain and behavioral aspects of verbal memory dysfunction in patients with schizophrenia through cognitive exercises. METHOD: Eight patients did daily verbal memory exercises that became progressively more difficult over a 10-week training period. Memory performance and regional brain activations during a verbal memory task were assessed before and after these exercises. RESULTS: Verbal but not nonverbal memory performance improved after training; three patients made substantial gains, and five showed little change. Performance gains were correlated with increases in task-related activation of the left inferior frontal cortex. One patient given 5 extra weeks of training 6 weeks after the initial training period showed maintenance of initial performance gains 6 weeks after training, further improvement after the second period of training, and normalization of task-related activation of the left inferior frontal cortex. CONCLUSIONS: Verbal memory deficits can be ameliorated by memory exercises in some patients with schizophrenia. Performance improvements are associated with increased task-related activation of the same brain region that is activated during verbal memory tasks in healthy individuals.

Adult↗

PubMed1999

Effect of estrogen on brain activation patterns in postmenopausal women during working memory tasks.

CONTEXT: Preclinical studies suggest that estrogen affects neural structure and function in mature animals; clinical studies are less conclusive with many, but not all, studies showing a positive influence of estrogen on verbal memory in postmenopausal women. OBJECTIVE: To investigate the effects of estrogen on brain activation patterns in postmenopausal women as they performed verbal and nonverbal working memory tasks. DESIGN: Randomized, double-blind, placebo-controlled, crossover trial from 1996 through 1998. SETTING: Community volunteers tested in a hospital setting. PATIENTS: Forty-six postmenopausal women aged 33 to 61 years (mean [SD] age, 50.8 [4.7] years). INTERVENTION: Twenty-one-day treatment with conjugated equine estrogens, 1.25 mg/d, randomly crossed over with identical placebo and a 14-day washout between treatments. MAIN OUTCOME MEASURES: Brain activation patterns measured using functional magnetic resonance imaging during tasks involving verbal and nonverbal working memory. RESULTS: Treatment with estrogen increased activation in the inferior parietal lobule during storage of verbal material and decreased activation in the inferior parietal lobule during storage of nonverbal material. Estrogen also increased activation in the right superior frontal gyrus during retrieval tasks, accompanied by greater left-hemisphere activation during encoding. The latter pattern represents a sharpening of the hemisphere encoding/retrieval asymmetry (HERA) effect. Estrogen did not affect actual performance of the verbal and nonverbal memory tasks. CONCLUSIONS: Estrogen in a therapeutic dosage alters brain activation patterns in postmenopausal women in specific brain regions during the performance of the sorts of memory function that are called upon frequently during any given day. These results suggest that estrogen affects brain organization for memory in postmenopausal women.

Adult↗

PubMed1999

Predicting midsagittal pharynx shape from tongue position during vowel production.

The shape of the pharynx has a large effect on the acoustics of vowels, but direct measurement of this part of the vocal tract is difficult. The present study examines the efficacy of inferring midsagittal pharynx shape from the position of the tongue, which is much more amenable to measurement. Midsagittal magnetic resonance (MR) images were obtained for multiple repetitions of 11 static English vowels spoken by two subjects (one male and one female). From these, midsagittal widths were measured at approximately 3-mm intervals along the entire vocal tract. A regression analysis was then used to assess whether the pharyngeal widths could be predicted from the locations and width measurements for four positions on the tongue, namely, those likely to be the locations of a receiver coil for an electromagnetometer system. Predictability was quite high throughout the vocal tract (multiple r> 0.9), except for the extreme ends (i.e., larynx and lips) and small decreases for the male subject in the uvula region. The residuals from this analysis showed that the accuracy of predictions was generally quite high, with 89.2% of errors being less than 2 mm. The extremes of the vocal tract, where the resolution of the MRI was poorer, accounted for much of the error. For languages like English, which do not use advanced tongue root (ATR) distinctively, the midsagittal pharynx shape of static vowels can be predicted with high accuracy.

Female↗

PubMed1998

Functional disruption in the organization of the brain for reading in dyslexia.

Learning to read requires an awareness that spoken words can be decomposed into the phonologic constituents that the alphabetic characters represent. Such phonologic awareness is characteristically lacking in dyslexic readers who, therefore, have difficulty mapping the alphabetic characters onto the spoken word. To find the location and extent of the functional disruption in neural systems that underlies this impairment, we used functional magnetic resonance imaging to compare brain activation patterns in dyslexic and nonimpaired subjects as they performed tasks that made progressively greater demands on phonologic analysis. Brain activation patterns differed significantly between the groups with dyslexic readers showing relative underactivation in posterior regions (Wernicke's area, the angular gyrus, and striate cortex) and relative overactivation in an anterior region (inferior frontal gyrus). These results support a conclusion that the impairment in dyslexia is phonologic in nature and that these brain activation patterns may provide a neural signature for this impairment.

Brain↗

PubMed1998

Cortical dysfunction in schizophrenia during auditory word and tone working memory demonstrated by functional magnetic resonance imaging.

BACKGROUND: Verbal learning and memory deficits are among the most severe cognitive deficits observed in schizophrenia. We have demonstrated that such deficits do not extend to working memory for tones in a substantial number of patients even when verbal working memory is impaired. In this study we used functional magnetic resonance imaging to study the neural basis of this dissociation of auditory verbal and nonverbal working memory in individuals with schizophrenia. METHODS: While undergoing functional magnetic resonance imaging, 12 schizophrenic patients and 12 matched control subjects performed auditory Word Serial Position Task and Tone Serial Position Task. RESULTS: Both tasks produced activation in frontal cortex and temporal and parietal lobes of the cerebrum in both groups. While robust activation was observed in the left inferior frontal gyrus (areas 6, 44, and 45) in the control group during the Word Serial Position Task, activation in the patient group was much reduced in these areas and failed to show the same task-specific activation as in controls. Reduced activation in patients was not confined to the inferior frontal gyrus, but also extended to a medial area during the Tone Serial Position Task and to premotor and anterior temporal lobe areas during both tasks. CONCLUSIONS: These findings support the hypothesis that abnormalities in cortical hemodynamic response in the inferior frontal gyrus underlie the verbal working memory deficit in schizophrenia. The relationship of verbal working memory deficits to other cognitive functions suggests that abnormal functioning in the speech-related areas may reflect a critical substrate of a broad range of cognitive dysfunctions associated with schizophrenia.

Adult↗

PubMed1998

Functional MRI studies of auditory comprehension.

The location of brain regions essential for auditory language comprehension is an important consideration in the planning of neurosurgical procedures that involve resections within the dominant temporal lobe. Language testing during intraoperative and extraoperative cortical stimulation has been the primary method for localizing these regions; however, noninvasive alternatives using functional neuroimaging have been sought. Here we report on a study of 14 subjects who listened passively to alternating sentences spoken in their native English language and in unfamiliar Turkish while functional magnetic resonance images were acquired. The English sentences produced strong activation within the left superior temporal sulcus in all subjects. Lesser activation was seen in homotopic right hemisphere locations in several subjects. In addition to these posterior temporal activations, 8 subjects also showed activation to English sentences in the left inferior frontal gyrus. Turkish sentences evoked no coherent region of activation in any subject. As both the Turkish and English sentences were read by the same speaker, and were matched for length, volume, and intonation, we conclude that the activation pattern evoked by the English sentences reflects auditory comprehension. This conclusion is further supported by additional control studies that have shown a markedly different pattern of activation by pure tone frequency glides.

Acoustic Stimulation↗

PubMed1998

Quantification of intravascular and extravascular contributions to BOLD effects induced by alteration in oxygenation or intravascular contrast agents.

A simple model is presented that allows quantitative separation of the contributions of signals from water in blood and extravascular parenchyma due to changes in blood oxygenation, induced either by brain activation or by alteration of inspired oxygen. The separation is based on the progressive attenuation of the signals in the vasculature of different levels when bipolar field gradient pulses are applied. Diffusion-weighted spin-echo echo-planar imaging sequences were used to measure signal changes under various conditions in both animals and human volunteers. Normoxic-hyperoxic episodes were induced in rats before and after injection of a superparamagnetic iron oxide contrast agent. Signal changes produced by visual stimulation were measured in human volunteers, and in volunteers subject to alternating normoxic-hyperoxic episodes, and with administration of Gd-DTPA. Analysis of the results with our simple model suggests that the apparent diffusion coefficient increases and R2 (= 1/T2) decreases upon brain activation, with a large component from extravascular water related to the decrease in the blood deoxyhemoglobin concentration. Furthermore, this study suggests that apparent diffusion coefficient of the extravascular component alone may provide localization of neuronal activation.

Animals↗

PubMed1998

Quantifying and comparing region-of-interest activation patterns in functional brain MR imaging: methodology considerations.

The general aims of functional brain magnetic resonance imaging (fMRI) studies are to ascertain which areas of the brain are activated during a specific task, the extent of this activation, whether different groups of subjects demonstrate different patterns of activation, and how these groups behave in different tasks. Many steps are involved in answering such questions and if each step is not carefully controlled the results may be influenced. This work has three objectives. Firstly, to present a technique for quantitatively evaluating methods used in functional imaging data analysis. While receiver-operator-characteristic (ROC) analysis has been used effectively to evaluate the ability of post-processing algorithms to detect true activations while rejecting false activations, it is difficult to adapt such a technique for comparisons of methods for quantitating activations. We present a technique based on the ANOVA, between two or more regions of interest (ROIs), subject groups, or activation tasks, over a range of statistical thresholds, which reveals the sensitivity of different activation quantification metrics to noise and other variables. Secondly, we use this technique to compare two methods of quantifying localized brain activation. There are numerous ways of quantifying the amount of activation present in a specific region of the brain in an individual subject. We compare the pixel count approach, which simply counts the number of pixels above an arbitrary statistical threshold, with an approach based on the sum of t-values above the same arbitrary t-value threshold. Finally, we examine the sensitivity of the results from an analysis of variance, to user defined parameters such as threshold and region of interest size. Both simulated and real functional magnetic resonance data are used to demonstrate these techniques.

Analysis of Variance↗

PubMed1998

MR of hereditary hemorrhagic telangiectasia: prevalence and spectrum of cerebrovascular malformations.

PURPOSE: Our goal was to describe the prevalence and types of cerebral vascular malformations (CVMs) seen with MR imaging in patients with hereditary hemorrhagic telangiectasia (HHT). METHODS: We reviewed retrospectively the brain MR images of 184 consecutive patients with HHT. Catheter angiography was performed in 17 patients with CVMs detected on MR images. RESULTS: MR imaging revealed 63 CVMs in 42 patients. Classic arteriovenous malformations (n = 10) had a conspicuous network of vessels with flow voids and enlarged adjacent pial vessels. Apparent venous malformations (n = 5) were best seen after administration of contrast material as a prominent vessel coursing through normal brain parenchyma. Indeterminate vascular malformations (n = 48) had a spectrum of appearances characterized by variable combinations of heterogeneous signal intensity, enhancement, or hemosiderin. Angiography in 17 patients revealed 47 CVMs. Forty-six were arteriovenous malformations (AVMs), including 25 CVMs not seen with MR imaging and 21 CVMs that by MR criteria included 8 AVMs and 13 indeterminate vascular malformations. Angiography confirmed 1 venous malformation seen with MR imaging but failed to detect 3 indeterminate lesions revealed by MR imaging. CONCLUSION: MR imaging of a large cohort of consecutive patients with HHT revealed a CVM prevalence of 23% (42/184). Most CVMs (48/63) have an atypical appearance for vascular malformations on MR images. Angiographic correlation suggests that MR imaging underestimates the prevalence of CVMs and that the majority of indeterminate CVMs, despite their variable MR appearance, are AVMs.

Cerebral Angiography↗