Biomedical subjects

K R Pugh

Publications and source records attributed to K R Pugh.

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 MRI of language processing: dependence on input modality and temporal lobe epilepsy.

PURPOSE: Functional magnetic resonance imaging (MRI) using two language-comprehension tasks was evaluated to determine its ability to lateralize language processing and identify regions that must be spared in surgery. METHODS: Two parallel cognitive language tasks, one using auditory input and the other visual input, were tested in a group of control subjects and in temporal lobe epilepsy patients who were candidates for surgical intervention. The patient studies provide an opportunity to compare functional MRI language localization with that obtained using Wada testing and electrocorticography. All of the patients in this study underwent all three procedures and a battery of neuropsychological testing. Such studies provide an opportunity not only to validate the fMRI findings but also, by comparing the patient results with those obtained in control subjects, to provide insight into the impact of a pathology such as epilepsy on cortical organization or functional patterns of activation. RESULTS: The results reveal both modality-dependent and modality-independent language-processing patterns for visual versus auditory task presentation. The visual language task activated distinct sites in Broca's area, BA (Brodmann area) 44 that were not activated in the auditory language task. The auditory language task strongly activated contralateral right BA22-21 area (homologous to Wernicke's area on the left). Language lateralization scores were significantly stronger for visual than for auditory task presentation. The conjunction of activation from the two different input modalities (modality-independent areas) likely highlights regions that perform more abstract computations (e.g., syntactic or pragmatic processing) in language processing. Modality-specific areas (e.g., right Wernicke, left fusiform gyrus, Broca BA44, supramarginal gyrus), appear to cope with the computations relevant to making contact with these more abstract dimensions. Patients showed recruitment of contralateral homologous language areas (p < 0.005) that was significantly above that found in a normal control group. Extra- and intraoperative cortical stimulations were concordant with the fMRI data in eight of 10 cases. The fMRI lateralization scores were also consistent with the Wada testing in 8/10 patients. CONCLUSIONS: The fMRI results demonstrate that the epileptic brain may be a progressive model for cortical plasticity.

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

Functional neuroimaging studies of reading and reading disability (developmental dyslexia).

Converging evidence from a number of neuroimaging studies, including our own, suggest that fluent word identification in reading is related to the functional integrity of two consolidated left hemisphere (LH) posterior systems: a dorsal (temporo-parietal) circuit and a ventral (occipito-temporal) circuit. This posterior system is functionally disrupted in developmental dyslexia. Reading disabled readers, relative to nonimpaired readers, demonstrate heightened reliance on both inferior frontal and right hemisphere posterior regions, presumably in compensation for the LH posterior difficulties. We propose a neurobiological account suggesting that for normally developing readers the dorsal circuit predominates at first, and is associated with analytic processing necessary for learning to integrate orthographic features with phonological and lexical-semantic features of printed words. The ventral circuit constitutes a fast, late-developing, word identification system which underlies fluent word recognition in skilled readers.

Cerebral Cortex↗

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

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↗

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

Persistence of dyslexia: the Connecticut Longitudinal Study at adolescence.

OBJECTIVE: The outcome in adolescence of children diagnosed as dyslexic during the early years of school was examined in children prospectively identified in childhood and continuously followed to young adulthood. This sample offers a unique opportunity to investigate a prospectively identified sample of adolescents for whom there is no question of the childhood diagnosis and in whom highly analytic measures of reading and language can be administered in adolescence. DESIGN: Children were recruited from the Connecticut Longitudinal Study, a cohort of 445 children representative of those children entering public kindergarten in Connecticut in 1983. Two groups were selected when the children were in grade 9: children who met criteria for persistent reading disability in grades 2 through 6 (persistently poor readers [PPR]; n = 21) and a comparison group of nondisabled children, subdivided into average readers (n = 35) and superior readers (n = 39). In grade 9, each child received a comprehensive assessment of academic, language, and other cognitive skills. RESULTS: Measures of phonological awareness (but not orthographic awareness) were most significant in differentiating the 3 reading groups, with smaller contributions from measures of word finding and digit-span. Academic measures that best separated good from poor readers were decoding and spelling, whereas measures of math and reading comprehension did not. Measures of phonological awareness, followed next by teacher rating of academic skills were the best predictors of decoding, reading rate, and reading accuracy. In contrast, the best predictor of reading comprehension was word finding, with digit span and socioeconomic status also contributing significantly. Using a growth curve model (quadratic model of growth to a plateau) all 3 groups demonstrated similar patterns of growth over time, with the superior group outperforming the average group, and the average group outperforming the PPR group. There was no evidence that the children in the PPR group catch up in their reading skills. CONCLUSIONS: Deficits in phonological coding continue to characterize dyslexic readers even in adolescence; performance on phonological processing measures contributes most to discriminating dyslexic and average readers, and average and superior readers as well. These data support and extend the findings of previous investigators indicating the continuing contribution of phonological processing to decoding words, reading rate, and accuracy and spelling. Children with dyslexia neither spontaneously remit nor do they demonstrate a lag mechanism for catching up in the development of reading skills. In adolescents, the rate of reading as well as facility with spelling may be most useful clinically in differentiating average from poor readers.

Adolescent↗

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

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↗

PubMed1997

Predicting reading performance from neuroimaging profiles: the cerebral basis of phonological effects in printed word identification.

This study linked 2 experimental paradigms for the analytic study of reading that heretofore have been used separately. Measures on a lexical decision task designed to isolate phonological effects in the identification of printed words were examined in young adults. The results were related to previously obtained measures of brain activation patterns for these participants derived from functional magnetic resonance imaging (fMRI). The fMRI measures were taken as the participants performed tasks that were designed to isolate orthographic, phonological, and lexical-semantic processes in reading. Individual differences in the magnitude of phonological effects in word recognition, as indicated by spelling-to-sound regularity effects on lexical decision latencies and by sensitivity to stimulus length effects, were strongly related to differences in the degree of hemispheric lateralization in 2 cortical regions.

Adult↗

PubMed1996

Auditory selective attention: an fMRI investigation.

In the present experiment, 25 adult subjects discriminated speech tokens ([ba]/[da]) or made pitch judgments on tone stimuli (rising/falling) under both binaural and dichotic listening conditions. We observed that when listeners performed tasks under the dichotic conditions, during which greater demands are made on auditory selective attention, activation within the posterior (parietal) attention system and at primary processing sites in the superior temporal and inferior frontal regions was increased. The cingulate gyrus within the anterior attention system was not influenced by this manipulation. Hemispheric differences between speech and nonspeech tasks were also observed, both at Broca's Area within the inferior frontal gyrus and in the middle temporal gyrus.

Adult↗

PubMed1996

Cerebral organization of component processes in reading.

The cerebral organization of word identification processes in reading was examined using functional magnetic resonance imaging (fMRI). Changes in fMRI signal intensities were measured in 38 subjects (19 males and 19 females) during visual (line judgement), orthographic (letter case judgement), phonological (nonword rhyme judgement) and semantic (semantic category judgement) tasks. A strategy of multiple subtractions was employed in order to validate relationships between structure and function. Orthographic processing made maximum demands on extrastriate sites, phonological processing on a number of frontal and temporal sites, and lexical-semantic processing was most strongly associated with middle and superior temporal sites. Significant sex differences in the cerebral organization of reading-related processes were also observed.

Adult↗

PubMed1995

Sex differences in the functional organization of the brain for language.

A much debated question is whether sex differences exist in the functional organization of the brain for language. A long-held hypothesis posits that language functions are more likely to be highly lateralized in males and to be represented in both cerebral hemispheres in females, but attempts to demonstrate this have been inconclusive. Here we use echo-planar functional magnetic resonance imaging to study 38 right-handed subjects (19 males and 19 females) during orthographic (letter recognition), phonological (rhyme) and semantic (semantic category) tasks. During phonological tasks, brain activation in males is lateralized to the left inferior frontal gyrus regions; in females the pattern of activation is very different, engaging more diffuse neural systems that involve both the left and right inferior frontal gyrus. Our data provide clear evidence for a sex difference in the functional organization of the brain for language and indicate that these variations exist at the level of phonological processing.

Adult↗

PubMed1994

A cohort model of visual word recognition.

A model of word recognition is proposed which assumes that when a word is encountered, the first available orthographic code activates all lexical entries that are positionally consistent with that information (i.e., the word's cohort). As subsequently encoded orthographic information becomes available, activation is withdrawn from lexical entries with which it is inconsistent, and the cohort is resolved when only a single candidate remains. The model is intended to characterize: (1) The initial encoding of the graphic information; (2) the recording of that information into an abstract orthographic form; (3) the manner in which the appropriate lexical entries are then activated; (4) the process whereby subsequent orthographic encoding resolves those activated entries to a single candidate; and finally (5) the way in which subjects use information for making decisions as it emerges during this processing. The model includes two critical points. The first is that letter identity information is encoded in the form of a complex orthographic unit termed a wickelgraph. A wickelgraph includes an encoding of the target letter's identity information as its core, plus, as a context, the identity of its two immediately adjacent letters. The set of possible wickelgraphs is assumed to instantiate the rules of orthography. The second point is that once a cohort is established, the perceiver can sample its status at any point during resolution and base a decision on the outcome of that sample. Some tasks (e.g., naming) may allow for a decision based on the initial status of the cohort, while others (e.g., lexical decision) can require its complete resolution. Six experiments are reported that illustrate some of these cohort effects in lexical access.

Attention↗

PubMed1994

Evidence of flexible coding in visual word recognition.

In 3 visual word recognition experiments, the authors examined Ss' differential dependence on phonological versus orthographic information in accessing the lexicon. The critical manipulation was the presence or absence of pseudohomophones in the nonword context of a lexical decision task. Ss received a list with either no pseudohomophones (NPsH group) or 17%-30% pseudohomophones among the nonwords (PsH group). In the first 2 experiments Ss in the PsH group were faster and no less accurate on word trials than Ss in the NPsH group. Furthermore, performance in the NPsH group was adversely affected by phonological inconsistency in the target's orthographic neighborhood. In the final experiment, a double lexical decision paradigm was used, and performance on orthographically similar but phonologically dissimilar pairs differed in the 2 conditions.

Humans↗

PubMed1994

Neighborhood effects in visual word recognition: effects of letter delay and nonword context difficulty.

The role of a target's orthographic neighborhood in visual word recognition was investigated in 2 lexical decision experiments. In both experiments, some stimuli had 1 letter delayed relative to the presentation of the rest of the stimulus. Experiment 1 showed that delaying a letter position, which yielded a potentially competitive neighbor, was more costly to target recognition than delaying a position that yielded no neighbors. This effect was strongest when one of these neighbors was of higher frequency than the target itself. Additionally, the effect was reduced for words with a high friendly-to-unfriendly-neighbor ratio (friendly neighbors being those words containing the delayed letter). In Experiment 2 the difficulty of the word-nonword discrimination was manipulated by varying the density of the nonwords' neighborhoods. Only when the nonwords had many neighbors at several positions did the word responses show neighborhood competition effects.

Decision Making↗

PubMedDate not supplied

Neurobiological studies of reading and reading disability.

UNLABELLED: Evidence from neuroimaging studies, including our own, suggest that skilled word identification in reading is related to the functional integrity of two consolidated left hemisphere (LH) posterior systems: a dorsal (temporo-parietal) circuit and a ventral (occipito-temporal) circuit. This posterior system appears to be functionally disrupted in developmental dyslexia. Relative to nonimpaired readers, reading-disabled individuals demonstrate heightened reliance on both inferior frontal and right hemisphere posterior regions, presumably in compensation for the LH posterior difficulties. We propose a neurobiological account suggesting that for normally developing readers, the dorsal circuit predominates at first, and in conjunction with premotor systems, is associated with analytic processing necessary for learning to integrate orthographic with phonological and lexical semantic features of printed words. The ventral circuit constitutes a fast, late-developing, word form system, which underlies fluency in word recognition. LEARNING OUTCOMES: As a result of this activity, (1) the participant will learn about a model of lexical processing involving specific cortical regions. (2) The participant will learn about evidence which supports the theory that two dorsal LH systems may be disrupted in developmental dyslexia. (3) The participant will learn that individuals with reading impairment may rely on other regions of the brain to compensate for the disruption of posterior function.

Brain↗