Biomedical subjects

C J Price

Publications and source records attributed to C J Price.

At least 19 recordsLinked to original sources

PubMed2006

How affected is oxygen metabolism in DWI lesions?: A combined acute stroke PET-MR study.

OBJECTIVE: To use back-to-back diffusion-weighted imaging (DWI) and PET to obtain quantitative measures of the cerebral metabolic rate of oxygen (CMRO(2)) within DWI lesions, and to assess the perfusion-metabolism coupling status by measuring the cerebral blood flow and the oxygen extraction fraction within DWI lesions. METHODS: Six prospectively recruited acute carotid-territory stroke patients completed the imaging protocol, which was commenced 7 to 21 hours from onset and combined DWI derived from state-of-the-art diffusion tensor imaging sequencing using a 3-T magnet and fully quantitative (15)O-PET. The PET variables were obtained in individual DWI lesions in each patient. RESULTS: Across patients, the CMRO(2) was reduced in the DWI lesion relative to mirror (mean reduction 39.5%; p = 0.028). Examining individual DWI lesions, however, revealed considerable variability in the extent of this CMRO(2) reduction. The flow-metabolism coupling pattern underlying the DWI lesion was also variable, including ongoing ischemia, mild oligemia, and partial or complete reperfusion. DISCUSSION: Diffusion-weighted imaging (DWI) lesions generally reflect substantial disruption of energy metabolism. However, the degree of metabolic disruption is variable, indicating DWI lesions may not always represent irreversibly damaged tissue. Finally, because DWI lesions can persist despite reperfusion, assessment of perfusion is necessary for interpretation of DWI changes in acute stroke.

Aged↗

PubMed2006

Language control in the bilingual brain.

How does the bilingual brain distinguish and control which language is in use? Previous functional imaging experiments have not been able to answer this question because proficient bilinguals activate the same brain regions irrespective of the language being tested. Here, we reveal that neuronal responses within the left caudate are sensitive to changes in the language or the meaning of words. By demonstrating this effect in populations of German-English and Japanese-English bilinguals, we suggest that the left caudate plays a universal role in monitoring and controlling the language in use.

Adult↗

PubMed2006

Human brain mechanisms for the early analysis of voices.

In this functional magnetic resonance imaging study, we investigated human brain mechanisms that are involved in the analysis of voices as sound sources and in the pre-semantic analysis of voice information. The source of the voice was altered by changing the speaker, and the salience of the voice was altered by changing the amount of spectrotemporal detail. We identified a mechanism for detecting a change in the source of the voice in the posterior superior temporal lobe and anatomically distinct mechanisms for the detailed analysis of voice information in a bilateral network extending from the posterior to the anterior superior temporal lobe surrounding the superior temporal sulcus. The findings are consistent with a processing hierarchy in which general source attributes are analyzed in the posterior superior temporal lobe, abstraction of voice identity features occurs in posterior superior temporal sulcus, and further analysis of voice information occurs in anterior superior temporal sulcus and higher order cortices in the middle and anterior temporal lobe.

Adult↗

PubMed2005

Action selectivity in parietal and temporal cortex.

The sensory-action theory proposes that the neural substrates underlying action representations are related to a visuomotor action system encompassing the left ventral premotor cortex, the anterior intraparietal (AIP) and left posterior middle temporal gyrus (LPMT). Using fMRI, we demonstrate that semantic decisions on action, relative to non-action words, increased activation in the left AIP and LPMT irrespective of whether the words were presented in a written or spoken form. Left AIP and LPMT might thus play the role of amodal semantic regions that can be activated via auditory as well as visual input. Left AIP and LPMT did not distinguish between different types of actions such as hand actions and whole body movements, although a right STS region responded selectively to whole body movements.

Acoustic Stimulation↗

PubMed2005

How reading differs from object naming at the neuronal level.

This paper uses whole brain functional neuroimaging in neurologically normal participants to explore how reading aloud differs from object naming in terms of neuronal implementation. In the first experiment, we directly compared brain activation during reading aloud and object naming. This revealed greater activation for reading in bilateral premotor, left posterior superior temporal and precuneus regions. In a second experiment, we segregated the object-naming system into object recognition and speech production areas by factorially manipulating the presence or absence of objects (pictures of objects or their meaningless scrambled counterparts) with the presence or absence of speech production (vocal vs. finger press responses). This demonstrated that the areas associated with speech production (object naming and repetitively saying "OK" to meaningless scrambled pictures) corresponded exactly to the areas where responses were higher for reading aloud than object naming in Experiment 1. Collectively the results suggest that, relative to object naming, reading increases the demands on shared speech production processes. At a cognitive level, enhanced activation for reading in speech production areas may reflect the multiple and competing phonological codes that are generated from the sublexical parts of written words. At a neuronal level, it may reflect differences in the speed with which different areas are activated and integrate with one another.

Adult↗

PubMed2004

An FMRI study of syntactic adaptation.

It is easier to produce and comprehend a series of sentences when they have similar syntactic structures. This "syntactic priming" effect was investigated during silent sentence reading using (i) blood oxygenation level-dependent (BOLD) response as a physiological measure in an f MRI study and (ii) reading time as a behavioral measure in a complementary self paced reading paradigm. We found that reading time and left anterior temporal activation were decreased when subjects read sentences with similar relative to dissimilar syntactic forms. Thus, syntactic adaptation during sentence comprehension is demonstrated in a neural area that has previously been linked to both lexical semantic and sentence processing.

Adaptation, Physiological↗

PubMed2003

Developmental toxicity evaluation of sodium thioglycolate administered topically to Sprague-Dawley (CD) rats and New Zealand White rabbits.

BACKGROUND: Sodium thioglycolate, which has widespread occupational and consumer exposure to women from cosmetics and hair-care products, was evaluated for developmental toxicity by topical exposure during the embryonic and fetal periods of pregnancy METHODS: Timed-mated Sprague-Dawley rats (25/group) and New Zealand White (NZW) rabbits (24/group) were exposed to sodium thioglycolate in vehicle (95% ethanol:distilled water, 1:1) by unoccluded topical application on gestational days (GD) 6-19 (rats) or 6-29 (rabbits) for 6 hr/day, at 0, 50, 100, or 200 mg/kg body weight/day (rats) and 0, 10, 15, 25, or 65 mg/kg/day (rabbits). At termination (GD 20 rats; GD 30 rabbits), fetuses were examined for external, visceral, and skeletal malformations and variations. RESULTS: In rats, maternal topical exposure to sodium thioglycolate, at 200 mg/kg/day (the highest dose tested) on GD 6-19, resulted in maternal toxicity, including reduced body weights and weight gain, increased relative water consumption and one death. Treatment-related increases in feed consumption and changes at the applicationsite occurred at all doses, in the absence of increased body weights or body weight change. Fetal body weights/litter were decreased at 200 mg/kg/day, with no other embryo/fetal toxicity and no treatment-related teratogenicity in any group. In rabbits, maternal topical exposure to sodium thioglycolate on GD 6-29 resulted in maternal dose-related toxicity at the dosing site in all groups; no maternal systemic toxicity, embryo/fetal toxicity, or treatment-related teratogenicity were observed in any group. CONCLUSIONS: A no observed adverse effect level (NOAEL) was not identified for maternal toxicity in either species with the dosages tested. The developmental toxicity NOAEL was 100 mg/kg/day (rats) and > or = 65 mg/kg/day (rabbits; the highest dose tested). The clinical relevance of theses study results is uncertain because no data were available for levels, frequency, or duration of exposures in female workers or end users.

Abnormalities, Drug-Induced↗

PubMed2003

Cortical localisation of the visual and auditory word form areas: a reconsideration of the evidence.

In this paper we examine the evidence for human brain areas dedicated to visual or auditory word form processing by comparing cortical activation for auditory word repetition, reading, picture naming, and environmental sound naming. Both reading and auditory word repetition activated left lateralised regions in the frontal operculum (Broca's area), posterior superior temporal gyrus (Wernicke's area), posterior inferior temporal cortex, and a region in the mid superior temporal sulcus relative to baseline conditions that controlled for sensory input and motor output processing. In addition, auditory word repetition increased activation in a lateral region of the left mid superior temporal gyrus but critically, this area is not specific to auditory word processing, it is also activated in response to environmental sounds. There were no reading specific activations, even in the areas previously claimed as visual word form areas: activations were either common to reading and auditory word repetition or common to reading and picture naming. We conclude that there is no current evidence for cortical sites dedicated to visual or auditory word form processing.

Adult↗

PubMed2002

The response of left temporal cortex to sentences.

The meaning of a sentence differs from the sum of the meanings of its constituents. Left anterior temporal cortex responds to sentences more strongly than to unconnected words. We hypothesized that the anterior temporal response to sentences is due to this difference in meaning (compositional semantics). Using positron emission tomography (PET), we studied four experimental conditions (2 x 2 factorial design): In one condition, subjects read normal sentences. In a second condition, they read grammatically correct sentences containing numerous semantic violations (semantically random sentences). In a third condition, we scrambled the word order within the normal sentences, and, in a fourth condition, the word order was scrambled within the semantically random sentences. The left anterior temporal pole responded strongly to sentences compared to scrambled versions of sentences. A similar although weaker response occurred in the left anterior superior temporal sulcus and the left posterior middle temporal gyrus. A subset of voxels within the left anterior temporal pole responded more to semantically random sentences and their scrambled versions than to normal sentences and the corresponding scrambled versions (main effect of semantic randomness). Finally, the grammatical and the semantic factor interacted in a subset of voxels within the anterior temporal pole: Activity was higher when subjects read normal sentences compared to their scrambled versions but not for semantically random sentences compared to their corresponding scrambled versions. The effects of grammar and meaning and, most importantly, the interaction between grammatical and semantic factors are compatible with the hypothesis that the left anterior temporal pole contributes to the composition of sentence meaning.

Adult↗

PubMed2002

Detecting latency differences in event-related BOLD responses: application to words versus nonwords and initial versus repeated face presentations.

We introduce a new method for detecting differences in the latency of blood oxygenation level-dependent (BOLD) responses to brief events within the context of the General Linear Model. Using a first-order Taylor approximation in terms of the temporal derivative of a canonical hemodynamic response function, statistical parametric maps of differential latencies were estimated via the ratio of derivative to canonical parameter estimates. This method was applied to two example datasets: comparison of words versus nonwords in a lexical decision task and initial versus repeated presentations of faces in a fame-judgment task. Tests across subjects revealed both magnitude and latency differences within several brain regions. This approach offers a computationally efficient means of detecting BOLD latency differences over the whole brain. Precise characterization of the hemodynamic latency and its interpretation in terms of underlying neural differences remain problematic, however.

Adult↗

PubMed2002

Anatomic constraints on cognitive theories of category specificity.

Many cognitive theories of semantic organization stem from reports of patients with selective, category-specific deficits for particular classes of objects (e.g., fruit). The anatomical assumptions underlying the competing claims can be evaluated with functional neuroimaging but the findings to date have been inconsistent and insignificant when standard statistical criteria are adopted. We hypothesized that category differences in functional brain responses might be small and task dependent. To test this hypothesis, we entered data from seven PET studies into a single multifactorial design which crossed category (living vs man-made) with a range of tasks. Reliable category-specific effects were observed but only for word retrieval and semantic decision tasks. Living things activated medial aspects of the anterior temporal poles bilaterally while tools activated a left posterior middle temporal region. These category-by-task interactions provide robust evidence for an anatomical double dissociation according to category and place strong constraints on cognitive theories of the semantic system. Furthermore they reconcile some of the apparent inconsistencies between lesion studies and functional neuroimaging data.

Adult↗

PubMed2002

A PET study of stimulus- and task-induced semantic processing.

To investigate the neural correlates of semantic processing, previous functional imaging studies have used semantic decision and generation tasks. However, in addition to activating semantic associations these tasks also involve executive functions that are not specific to semantics. The study reported in this paper aims to dissociate brain activity due to stimulus-driven semantic associations and task-induced semantic and executive processing by using repetition and semantic decision on auditorily presented words in a cognitive conjunction design. The left posterior inferior temporal, inferior frontal (BA 44/45), and medial orbital gyri were activated by both tasks, suggesting a general role in stimulus-driven semantic and phonological processing. In addition, semantic decision increased activation in (i) left ventral inferior frontal cortex (BA 47), right cerebellum, and paracingulate, which have all previously been implicated in executive functions, and (ii) a ventral region in the left anterior temporal pole which is commonly affected in patients with semantic impairments. We attribute activation in this area to the effortful linkage of semantic features. Thus, our study replicated the functional dissociation between dorsal and ventral regions of the left inferior frontal cortex. Moreover, it also dissociated the semantic functions of the left posterior inferior temporal gyrus and anterior temporal pole: The posterior region subserves stimulus-driven activation of semantic associations and the left anterior region is involved in task-induced association of semantic information.

Adult↗

PubMed2002

Retrieval of visual, auditory, and abstract semantics.

Conceptual knowledge is thought to be represented in a large distributed network, indexing a range of different semantic features (e.g., visual, auditory, functional). We investigated the anatomical organization of these features, using PET, by contrasting brain activity elicited by heard words with (i) visual (e.g., blue), (ii) auditory (e.g., noise), or (iii) abstract (e.g., truth) meaning. The activation task was either repetition or semantic decision (e.g., does the meaning of the word relate to religion?). In the baseline conditions, the sound track of the words was reversed and subjects had to say "OK" (control for repetition) or make an acoustic decision (control for semantic decision). Irrespective of task, words relative to their corresponding controls activated the left posterior inferior temporal and inferior frontal cortices. In addition, semantic decisions on words with sensory (visual and auditory) meanings enhanced activation in a ventral region of the left anterior temporal pole. These results are consistent with neuropsychological studies showing that anterior temporal lobe damage can cause deficits for items that are mainly defined by their sensory features (i.e., concrete, particularly living items). Since modality-specific activation was observed only during the semantic decision task, we discuss whether it reflects retrieval of sensory semantics per se or the degree to which semantic associations are triggered during effortful retrieval.

Adult↗

PubMed2001

The constraints functional neuroimaging places on classical models of auditory word processing.

Several previous functional imaging experiments have demonstrated that auditory presentation of speech, relative to tones or scrambled speech, activate the superior temporal sulci (STS) bilaterally. In this study, we attempted to segregate the neural responses to phonological, lexical, and semantic input by contrasting activation elicited by heard words, meaningless syllables, and environmental sounds. Inevitable differences between the duration and amplitude of each stimulus type were controlled with auditory noise bursts matched to each activation stimulus. Half the subjects were instructed to say "okay" in response to presentation of all stimuli. The other half repeated back the words and syllables, named the source of the sounds, and said "okay" to the control stimuli (noise bursts). We looked for stimulus effects that were consistent across task. The results revealed that central regions in the STS were equally responsive to speech (words and syllables) and familiar sounds, whereas the posterior and anterior regions of the left superior temporal gyrus were more active for speech. The effect of semantic input was small but revealed more activation in the inferior temporal cortex for words and familiar sounds than syllables and noise. In addition, words (relative to syllables, sounds, and noise) enhanced activation in the temporo-parietal areas that have previously been linked to modality independent semantic processing. Thus, in cognitive terms, we dissociate phonological (speech) and semantic responses and propose that word specificity arises from functional integration among shared phonological and semantic areas.

Adult↗

PubMed2001

The effects of case mixing on word recognition: evidence from a PET study.

The early stages of visual word recognition were investigated by scanning participants using PET as they took part in implicit and explicit reading tasks with visually disrupted stimuli. CaSe MiXiNg has been shown in behavioral studies to increase reaction times (RTs) in naming and other word recognition tasks. In this study, we found that during both an implicit (feature detection) task and an explicit word-naming task, mixed-case words compared to same-case words produced increased activation in an area of the right parietal cortex previously associated with visual attention. No effect of case was found in this area for pseudowords or consonant strings. Further, lowering the contrast of the stimuli slowed RTs as much as case mixing, but did not lead to the same increase in right parietal activation. No significant effect of case mixing was observed in left-hemisphere language areas. The results suggest that reading mixed-case words requires increased attentional processing. However, later word recognition processes may be relatively unaffected by the disruption in presentation.

Attention↗

PubMed2001

Dynamic diaschisis: anatomically remote and context-sensitive human brain lesions.

Functional neuroimaging was used to investigate how lesions to the Broca's area impair neuronal responses in remote undamaged cortical regions. Four patients with speech output problems, but relatively preserved comprehension, were scanned while viewing words relative to consonant letter strings. In normal subjects, this results in left lateralized activation in the posterior inferior frontal, middle temporal, and posterior inferior temporal cortices. Each patient activated normally in the middle temporal region but abnormally in the damaged posterior inferior frontal cortex and the undamaged posterior inferior temporal cortex. In the damaged frontal region, activity was insensitive to the presence of words but in the undamaged posterior inferior temporal region, activity decreased in the presence of words rather than increasing as it did in the normal individuals. The reversal of responses in the left posterior inferior temporal region illustrate the context-sensitive nature of the abnormality and that failure to activate the left posterior temporal region could not simply be accounted for by insufficient demands on the underlying function. We propose that, in normal individuals, visual word presentation changes the effective connectivity among reading areas and, in patients, posterior temporal responses are abnormal when they depend upon inputs from the damaged inferior frontal cortex. Our results serve to introduce the concept of dynamic diaschisis; the anatomically remote and context-sensitive effects of focal brain lesions. Dynamic diaschisis reveals abnormalities of functional integration that may have profound implications for neuropsychological inference, functional anatomy and, vicariously, cognitive rehabilitation.

Aphasia, Broca↗

PubMed2001

Assessing study-specific regional variations in fMRI signal.

In this paper, we present a post hoc method for identifying regions where functional MRI data are subject to signal reduction that may compromise sensitivity to activations. The motivation for developing this technique derives from recent language studies that showed responses in the inferior temporal lobe that could be detected by PET but not by fMRI. Reduced signal is due mostly to susceptibility artifacts and can be identified by comparing the T2* images (which are subject to susceptibility artifacts) with T2 images (which are not). However, T2 images are not usually acquired in fMRI studies. Therefore, we propose that areas with reduced signal can be identified by comparing T2* images that are corrected for nonuniformity with the original uncorrected images. The technique provides a voxel-wise characterization of signal reduction that pertains to the particular data that enter into a statistical model. It requires only the functional data and can thus be applied post hoc and without any additional scans.

Artifacts↗

PubMed2001

Voxel-based morphometry of herpes simplex encephalitis.

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

Adult↗