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P A Carpenter

Publications and source records attributed to P A Carpenter.

At least 19 recordsLinked to original sources
PubMed2001

fMRI investigation of sentence comprehension by eye and by ear: modality fingerprints on cognitive processes.

The neural substrate underlying reading vs. listening comprehension of sentences was compared using fMRI. One way in which this issue was addressed was by comparing the patterns of activation particularly in cortical association areas that classically are implicated in language processing. The precise locations of the activation differed between the two modalities. In the left inferior frontal gyrus (Broca's area), the activation associated with listening was more anterior and inferior than the activation associated with reading, suggesting more semantic processing during listening comprehension. In the left posterior superior and middle temporal region (roughly, Wernicke's area), the activation for listening was closer to primary auditory cortex (more anterior and somewhat more lateral) than the activation for reading. In several regions, the activation was much more left lateralized for reading than for listening. In addition to differences in the location of the activation, there were also differences in the total amount of activation in the two modalities in several regions. A second way in which the modality comparison was addressed was by examining how the neural systems responded to comprehension workload in the two modalities by systematically varying the structural complexity of the sentences to be processed. Here, the distribution of the workload increase associated with the processing of additional structural complexity was very similar across the two input modalities. The results suggest a number of subtle differences in the cognitive processing underlying listening vs. reading comprehension.

Adult↗
PubMed2001

Baseline conditions and subtractive logic in neuroimaging.

Discrepancies in the patterns of cortical activation across studies may be attributable, in part, to differences in baseline tasks, and hence, reflect the limits of the subtractive logic underlying much of neuroimaging. To assess the extent of these effects, three of the most commonly used baseline conditions (rest, tone monitoring, and passive listening) were compared using phoneme discrimination as the experimental task. Eight participants were studied in a fMRI study with a 4.1 T system. The three baseline conditions systematically affected the amount of activation observed in the identical phoneme task with major affects in Broca's area, the left posterior superior temporal gyrus, and the left and right inferior parietal regions. Two central findings were: 1) a differential effect of baseline within each region, with the rest baseline condition producing the greatest amount of activation and the passive listening condition producing the least, and 2) systematic baseline task activation in the inferior parietal regions. These results emphasize the relativity of activation patterns observed in functional neuroimaging, and the necessity to specify the baseline processes in context to the experimental task processes.

Adult↗
PubMed2001

Interdependence of nonoverlapping cortical systems in dual cognitive tasks.

One of the classic questions about human thinking concerns the limited ability to perform two cognitive tasks concurrently, such as a novice driver's difficulty in simultaneously driving and conversing. Limitations on the concurrent performance of two unrelated tasks challenge the tacitly assumed independence of two brain systems that seemingly have little overlap. The current study used fMRI (functional magnetic resonance imaging) to measure cortical activation during the concurrent performance of two high-level cognitive tasks that involve different sensory modalities and activate largely nonoverlapping areas of sensory and association cortex. One task was auditory sentence comprehension, and the other was the mental rotation of visually depicted 3-D objects. If the neural systems underlying the two tasks functioned independently, then in the dual task the brain activation in the main areas supporting the cognitive processing should be approximately the conjunction of the activation for each of the two tasks performed alone. We found instead that in the dual task, the activation in association areas (primarily temporal and parietal areas of cortex) was substantially less than the sum of the activation when the two tasks were performed alone, suggesting some mutual constraint among association areas. A similar result was obtained for sensory areas as well.

Adolescent↗
PubMed2001

Mental rotation of objects retrieved from memory: a functional MRI study of spatial processing.

This functional MRI study examined how people mentally rotate a 3-dimensional object (an alarm clock) that is retrieved from memory and rotated according to a sequence of auditory instructions. We manipulated the geometric properties of the rotation, such as having successive rotation steps around a single axis versus alternating between 2 axes. The latter condition produced much more activation in several areas. Also, the activation in several areas increased with the number of rotation steps. During successive rotations around a single axis, the activation was similar for rotations in the picture plane and rotations in depth. The parietal (but not extrastriate) activation was similar to mental rotation of a visually presented object. The findings indicate that a large-scale cortical network computes different types of spatial information by dynamically drawing on each of its components to a differential, situation-specific degree.

Adult↗
PubMed2001

The neural bases of sentence comprehension: a fMRI examination of syntactic and lexical processing.

One of the challenges to functional neuroimaging is to understand how the component processes of reading comprehension emerge from the neural activity in a network of brain regions. In this study, functional magnetic resonance imaging (fMRI) was used to examine lexical and syntactic processing in reading comprehension by independently manipulating the cognitive demand on each of the two processes of interest. After establishing a consistency with earlier research showing the involvement of the left perisylvian language areas in both lexical access and syntactic processing, the study produced new findings that are surprising in two ways: (i) the lexical and syntactic factors each impact not just individual areas, but they affect the activation in a network of left-hemisphere areas, suggesting that changing the computational load imposed by a given process produces a cascade of effects in a number of collaborating areas; and (ii) the lexical and syntactic factors usually interact in determining the amount of activation in each affected area, suggesting that comprehension processes that operate on different levels of language may nevertheless draw on a shared infrastructure of cortical resources. The results suggest that many processes in sentence comprehension involve multiple brain regions, and that many brain regions contribute to more than one comprehension process. The implication is that the language network consists of brain areas which each have multiple relative specializations and which engage in extensive interarea collaborations.

Adolescent↗
PubMed2000

Non-Fc receptor-binding humanized anti-CD3 antibodies induce apoptosis of activated human T cells.

Human trials in organ allografts have demonstrated that murine anti-CD3 mAbs are immunosuppressive. By mimicking Ag, anti-CD3 can produce T cell activation, anergy, or death. Activation of resting T cells in vivo results in dose-limiting cytokine release and is caused by Ab-mediated cross-linking of T cells and Fcgamma receptor (FcR)-bearing cells. With the goal of minimizing cytokine-induced toxicity, anti-CD3 have been engineered to lower Fc binding avidity. Preclinical murine studies have indicated that non-FcR-binding anti-CD3 can induce apoptosis of Ag-activated T cells. Since induction of T cell apoptosis may be an important mechanism of immunosuppression by anti-CD3, we tested whether Fc mutations affect the ability of anti-human CD3 to induce apoptosis of activated T cells. We compared wild-type murine anti-CD3, M291, and OKT3 and their humanized, FcR- and non-FcR-binding structural variants in quantitative assays of T cell apoptosis. Non-FcR-binding variants produced more sustainable phosphorylation of extracellular signal-regulated kinase-2, greater release of IFN-gamma, and more effectively caused activation-dependent T cell apoptosis. Non-FcR-binding variants dissociated more quickly from the T cell surface and caused less internalization of the TCR, which then remained available in greater abundance on the cell surface for signaling. Cross-linking of non-FcR-binding variants by antiglobulin enhanced TCR internalization and minimized induction of T cell apoptosis. We conclude that non-FcR-binding, humanized anti-CD3 have improved ability to induce apoptosis of activated T cells, presumably by allowing durable expression of the TCR and sustained signaling.

Adult↗
PubMed2000

The neural bases of strategy and skill in sentence-picture verification.

This experiment used functional Magnetic Resonance Imaging to examine the relation between individual differences in cognitive skill and the amount of cortical activation engendered by two strategies (linguistic vs. visual-spatial) in a sentence-picture verification task. The verbal strategy produced more activation in language-related cortical regions (e.g., Broca's area), whereas the visual-spatial strategy produced more activation in regions that have been implicated in visual-spatial reasoning (e.g., parietal cortex). These relations were also modulated by individual differences in cognitive skill: Individuals with better verbal skills (as measured by the reading span test) had less activation in Broca's area when they used the verbal strategy. Similarly, individuals with better visual-spatial skills (as measured by the Vandenberg, 1971, mental rotation test) had less activation in the left parietal cortex when they used the visual-spatial strategy. These results indicate that language and visual-spatial processing are supported by partially separable networks of cortical regions and suggests one basis for strategy selection: the minimization of cognitive workload.

Adolescent↗
PubMed2000

Collaborative activity between parietal and dorso-lateral prefrontal cortex in dynamic spatial working memory revealed by fMRI.

Functional MRI was used to determine how the constituents of the cortical network subserving dynamic spatial working memory respond to two types of increases in task complexity. Participants mentally maintained the most recent location of either one or three objects as the three objects moved discretely in either a two- or three-dimensional array. Cortical activation in the dorsolateral prefrontal (DLPFC) and the parietal cortex increased as a function of the number of object locations to be maintained and the dimensionality of the display. An analysis of the response characteristics of the individual voxels showed that a large proportion were activated only when both the variables imposed the higher level of demand. A smaller proportion were activated specifically in response to increases in task demand associated with each of the independent variables. A second experiment revealed the same effect of dimensionality in the parietal cortex when the movement of objects was signaled auditorily rather than visually, indicating that the additional representational demands induced by 3-D space are independent of input modality. The comodulation of activation in the prefrontal and parietal areas by the amount of computational demand suggests that the collaboration between areas is a basic feature underlying much of the functionality of spatial working memory.

Acoustic Stimulation↗
PubMed2000

Working memory and executive function: evidence from neuroimaging.

Traditional theories of working memory and executive function, when mapped in straightforward ways into the neural domain, yield predictions that are only partly supported by the recent neuroimaging studies. Neuroimaging studies suggest that some constituent functions, such as maintaining information in active form and manipulating it, are not discretely localized in prefrontal regions. Some hypothesized executive processes, such as goal management, have effects in several cortical regions, including posterior regions. Such results suggest a more dynamic and distributed view of the cortical organization of working memory and executive functions.

Brain Mapping↗
PubMed1999

Time course of fMRI-activation in language and spatial networks during sentence comprehension.

Functional neuroimaging previously has been considered to provide inadequate temporal resolution to study changes of brain states as a function of cognitive computations; however, we have obtained evidence of differential amounts of brain activity related to high-level cognition (sentence processing) within 1.5 s of stimulus onset. The study used an event-related paradigm with high-speed echoplanar functional magnetic resonance imaging (fMRI) to trace the time course of the brain activation in the temporal and parietal regions as participants comprehended single sentences describing a spatial configuration. Within the first set of images, on average 1 s from when the participant begins to read a sentence, there was significant activation in a key cortical area involved in language comprehension (the left posterior temporal gyrus) and visuospatial processing (the left and right parietal regions). In all three areas, the amount of activation during sentence comprehension was higher for negative sentences than for their affirmative counterparts, which are linguistically less complex. The effect of negation indicates that the activation in these areas is modulated by the difficulty of the linguistic processing. These results suggest a relatively rapid coactivation in both linguistic and spatial cortical regions to support the integration of information from multiple processing streams.

Adult↗
PubMed1999

Haemophagocytic lymphohistiocytosis in children.

OBJECTIVE: To evaluate the clinical and diagnostic features of children presenting with haemophagocytic lymphohistiocytosis (HLH), evolution of the disease and outcomes in response to treatment. METHODOLOGY: The medical records of 12 children, aged 5 weeks to 13 years at diagnosis, with HLH managed at a single institution were reviewed. RESULTS: Presenting features were fever, hepatosplenomegaly, pancytopenia and hypertriglyceridemia or hypofibrinogenemia. Nine patients (75%) developed central nervous system (CNS) disease. Only one child with CNS disease survived. Five children had complete responses to therapy (42%), but all relapsed at a median of 1.5 months after starting treatment (range 2 weeks to 5 months). Two of the children treated are long-term survivors (17%), both after allogeneic bone marrow transplantation. All deaths occurred in the context of active disease. CONCLUSIONS: Haemophagocytic lymphohistiocytosis is a disease with a poor prognosis. Central nervous system complications are common and response to treatment usually is transient. This study provides support for the use of immunomodulatory therapy for remission introduction followed by consideration of allogeneic bone marrow transplantation.

Adolescent↗
PubMed1999

Modeling the mind: very-high-field functional magnetic resonance imaging activation during cognition.

This article describes how fMRI can be used to examine the large-scale networks of cortical areas that subserve high-level cognition, such as sentence comprehension and visual thinking. The findings from a number of studies show that the qualitative and quantitative nature of the cognitive processes determines which cortical areas are activated (the network constituency) and the degree to which each network member is activated. For example, during sentence comprehension, activation in the left posterior temporal region and the inferior frontal gyrus, as well as their right hemisphere homologs, increases as a function of the linguistic complexity of the sentence. Such findings indicate that cognition emerges from the collaboration among the multiple cortical areas that compose the large-scale networks, rather than from the aggregate of autonomously functioning modules. The patterns of activation also show systematic shifts in the activity of a network during the spontaneous recovery of function by stroke patients, demonstrating cortical plasticity in adults. Finally, the article describes some simulation models that relate the information processing activity of a computational system to its resource consumption. This construct enables a mapping from the functional properties of the cognitive systems to the biological substrate that is reflected in fMRI.

Adult↗
PubMed1999

Plasticity of language-related brain function during recovery from stroke.

BACKGROUND AND PURPOSE: This study was undertaken to correlate functional recovery from aphasia after acute stroke with the temporal evolution of the anatomic, physiological, and functional changes as measured by MRI. METHODS: Blood oxygenation level-dependent contrast and echo-planar MRI were used to map language comprehension in 6 normal adults and in 2 adult patients during recovery from acute stroke presenting with aphasia. Perfusion, diffusion, sodium, and conventional anatomic MRI were used to follow physiological and structural changes. RESULTS: The normal activation pattern for language comprehension showed activation predominately in left-sided Wernicke's and Broca's areas, with laterality ratios of 0.8 and 0.3, respectively. Recovery of the patient confirmed as having a completed stroke affecting Broca's area occurred rapidly with a shift of activation to the homologous region in the right hemisphere within 3 days, with continued rightward lateralization over 6 months. In the second patient, in whom mapping was performed fortuitously before stroke, recovery of a Wernicke's aphasia showed a similar increasing rightward shift in activation recruitment over 9 months after the event. CONCLUSIONS: Recovery of aphasia in adults can occur rapidly and is concomitant with an activation pattern that changes from left to a homologous right hemispheric pattern. Such recovery occurs even when the stroke evolves to completion. Such plasticity must be considered when evaluating stroke interventions based on behavioral and neurological measurements.

Adult↗
PubMed1999

Graded functional activation in the visuospatial system with the amount of task demand.

Two studies examined how the amount and type of computational demand are related to fMRI-measured activation in three bilateral cortical regions involved in the Shepard-Metzler (1971) mental-rotation paradigm. The amount of demand for the computation of visuospatial coordinates was manipulated by presenting mental rotation problems with increasing angular disparity (0, 40, 80, or 120 degrees). Activation in both the left and right intraparietal sulcal regions increased linearly with angular disparity in two separate studies. Activation also occurred in the fusiform gyrus and inferior temporal regions, regions that are primarily associated with the processes of object and object-part identification. By contrast, the demand for object recognition and rotation processes was relatively low, and the demand for executing saccades was high in a control condition that required making a systematic visual scan of two grids. The grid-scanning condition resulted in relatively less activation in the parietal and inferior temporal regions but considerable activation in frontal areas that are associated with planning and executing saccades, including the precentral gyrus and sulcus into the posterior middle frontal region. These data suggest that the amount of activation in the various cortical regions that support visuospatial processing is related to the amount, as well as to the type, of computational demand.

Brain Mapping↗
PubMed1999

Computational modeling of high-level cognition and brain function.

This article describes a computational modeling architecture, 4CAPS, which is consistent with key properties of cortical function and makes good contact with functional neuroimaging results. Like earlier cognitive models such as SOAR, ACT-R, 3CAPS, and EPIC, the proposed cognitive model is implemented in a computer simulation that predicts observable variables such as human response times and error patterns. In addition, the proposed 4CAPS model accounts for the functional decomposition of the cognitive system and predicts fMRI activation levels and their localization within specific cortical regions, by incorporating key properties of cortical function into the design of the modeling system.

Brain↗
PubMed1997

A dose-intensive, cyclophosphamide-based regimen for the treatment of recurrent/progressive or advanced solid tumors of childhood: a report from the Australia and New Zealand Children's Cancer Study Group.

BACKGROUND: Children with solid tumors that progress or recur after conventional multimodality therapies have a very poor prognosis. In a pilot study, vincristine, etoposide, and dose-escalated cyclophosphamide (VETOPEC) was shown to be a promising salvage regimen. Continued accrual of patients and increased duration of follow-up has resulted in substantial experience with VETOPEC. METHODS: Between May 1991 and March 1994, 56 pediatric patients from 6 centers were enrolled in this study; 44 had recurrent or progressive tumors (Group A) and 12 had newly diagnosed, advanced tumors with a very poor prognosis (Group B). The VETOPEC regimen was comprised of vincristine, 0.05 mg/kg, on Days 1 and 14; etoposide, 2.5 mg/kg, on Days 1, 2, and 3; and fractionated, dose-escalated cyclophosphamide on Days 1, 2, and 3. The initial cyclophosphamide dose was 90 mg/kg (2.7 g/m2)/cycle with an escalation of 15 mg/kg/cycle in each subsequent cycle, to a maximum (over 6 cycles) of 165 mg/kg (5.0 g/m2)/cycle. Tumor response was evaluated every two to three cycles and included central review of imaging. RESULTS: The combined and partial response rates for Groups A and B were 66% (25 of 38 patients) and 91% (10 of 11 patients), respectively. In Group A, best evaluable responses and event free (EF) survivors were observed with: brain tumors (7 of 9 patients; 2 EF at 39 and 45 months [mos], respectively), Wilms' tumor (6 of 7 patients; 3 EF at 37-49 mos), and lymphoma (4 of 4 patients; 2 EF at 52 and 59 mos, respectively); in Group B best evaluable responses and EF were observed with: neuroblastoma (5 of 6 patients; 1 disease free at 57 mos) and rhabdomyosarcoma (4 of 4 patients; no survivors). Hematologic toxicity was limiting despite support with myeloid growth factors in 33 patients. Four deaths in Group A and one in Group B were directly associated with this toxicity. Specifically, no cases of drug-related myocardial toxicity or pneumonitis were observed. CONCLUSIONS: This chemotherapy regimen with its intense scheduling produced a high response rate and appreciable survival in patients with a variety of recurrent, progressive, or advanced solid tumors of childhood.

Adolescent↗
PubMed1997

Aphasic sentence comprehension as a resource deficit: a computational approach.

This article describes a new computational model of aphasic sentence comprehension. The model is based on the premise that all aphasics, however different, share a common deficit which determines a considerable amount of the individual variation observed in their sentence comprehension performance. This common deficit is construed as a pathological reduction in the activation resources of a working memory system that subserves sentence comprehension (Miyake, Carpenter, & Just, 1994). To test the theoretical feasibility of the resource reduction hypothesis, a new computer model of aphasic sentence comprehension was developed and tested. We describe the model as well as some initial simulation results, indicating that the model can account for some of the sentence complexity and severity effects that have been reported in the aphasia literature.

Aphasia↗