Biomedical subjects

Cathy J Price

Publications and source records attributed to Cathy J Price.

13 recordsLinked to original sources

PubMed2003

Effects of visual deprivation on the organization of the semantic system.

Early onset blindness provides a lesion model to investigate whether experience-dependent mechanisms subtend the functional anatomy of semantic retrieval. In particular, visual deprivation might alter the neural systems underlying retrieval of semantic information that is acquired via visual experience. Using functional MRI, we demonstrate that both early blind and sighted subjects activate a left-lateralized fronto-temporal 'core' semantic retrieval system and show common effects for retrieval of visually experienced semantic information. However, irrespective of the type of semantics, blind subjects activate additional extrastriate regions, which are coupled with frontal and temporal semantic regions. The resilience of semantic retrieval responses to visual deprivation suggests a considerable degree of innate and epigenetic specification of the semantic system. In contrast, the exuberant functional connectivity between extrastriate and 'core' semantic retrieval regions might be explained by abnormal pruning processes during early neurodevelopment.

Adult↗

PubMed2003

Neuroimaging studies of word and pseudoword reading: consistencies, inconsistencies, and limitations.

Several functional neuroimaging studies have compared words and pseudowords to test different cognitive models of reading. There are difficulties with this approach, however, because cognitive models do not make clear-cut predictions at the neural level. Therefore, results can only be interpreted on the basis of prior knowledge of cognitive anatomy. Furthermore, studies comparing words and pseudowords have produced inconsistent results. The inconsistencies could reflect false-positive results due to the low statistical thresholds applied or confounds from nonlexical aspects of the stimuli. Alternatively, they may reflect true effects that are inconsistent across subjects; dependent on experimental parameters such as stimulus rate or duration; or not replicated across studies because of insufficient statistical power. In this fMRI study, we investigate consistent and inconsistent differences between word and pseudoword reading in 20 subjects, and distinguish between effects associated with increases and decreases in activity relative to fixation. In addition, the interaction of word type with stimulus duration is explored. We find that words and pseudowords activate the same set of regions relative to fixation, and within this system, there is greater activation for pseudowords than words in the left frontal operculum, left posterior inferior temporal gyrus, and the right cerebellum. The only effects of words relative to pseudowords consistent over subjects are due to decreases in activity for pseudowords relative to fixation; and there are no significant interactions between word type and stimulus duration. Finally, we observe inconsistent but highly significant effects of word type at the individual subject level. These results (i) illustrate that pseudowords place increased demands on areas that have previously been linked to lexical retrieval, and (ii) highlight the importance of including one or more baselines to qualify word type effects. Furthermore, (iii) they suggest that inconsistencies observed in the previous literature may result from effects arising from a small number of subjects only.

Adult↗

PubMed2003

The anatomy and time course of semantic priming investigated by fMRI and ERPs.

We combined complementary non-invasive brain imaging techniques with behavioural measures to investigate the anatomy and time course of brain activity associated with semantic priming in a lexical-decision task. Participants viewed pairs of stimuli, and decided whether the second item was a real word or not. There were two variables, the semantic relationship between the prime and the target (related or unrelated) and the interval between the onset of prime and target (200 or 1000 ms), to vary the degree of semantic expectancy that was possible during task performance. Behavioural results replicated the well-established finding that identification of the target is facilitated by a preceding semantically related prime. Event-related functional magnetic resonance imaging (efMRI) identified two brain areas involved in the semantic-priming effect. Activity in the anterior medial temporal cortex was diminished when target words were primed by semantically related words, suggesting involvement of this brain region during active semantic association or integration. In contrast, activity in the left supramarginal gyrus in the temporal-parietal junction was enhanced for target words primed by semantically related words. Brain areas influenced by the interval between prime and target words, and by the interaction between word interval and semantic priming were also identified. A parallel experiment using event-related potentials (ERPs) unveiled a striking difference in the time course of semantic priming as a function of expectancy. In line with previous reports, the primary effect of semantic priming on ERPs was the attenuation of the N400 component, in both short- and long-interval conditions. However, the priming effect started significantly earlier in the long-interval condition. Activity in the anterior medial temporal cortex has previously been shown to contribute to the N400 component, a finding that links the priming results obtained with efMRI and ERP methods.

Adult↗

PubMed2003

Functional imaging of the semantic system: retrieval of sensory-experienced and verbally learned knowledge.

This paper considers how functional neuro-imaging can be used to investigate the organization of the semantic system and the limitations associated with this technique. The majority of the functional imaging studies of the semantic system have looked for divisions by varying stimulus category. These studies have led to divergent results and no clear anatomical hypotheses have emerged to account for the dissociations seen in behavioral studies. Only a few functional imaging studies have used task as a variable to differentiate the neural correlates of semantic features more directly. We extend these findings by presenting a new study that contrasts tasks that differentially weight sensory (color and taste) and verbally learned (origin) semantic features. Irrespective of the type of semantic feature retrieved, a common semantic system was activated as demonstrated in many previous studies. In addition, the retrieval of verbally learned, but not sensory-experienced, features enhanced activation in medial and lateral posterior parietal areas. We attribute these "verbally learned" effects to differences in retrieval strategy and conclude that evidence for segregation of semantic features at an anatomical level remains weak. We believe that functional imaging has the potential to increase our understanding of the neuronal infrastructure that sustains semantic processing but progress may require multiple experiments until a consistent explanatory framework emerges.

Adult↗

PubMed2003

Comparing event-related and epoch analysis in blocked design fMRI.

In this study we demonstrate that, even in blocked design fMRI, an event-related analysis may provide a more accurate model of the hemodynamic responses than an epoch-related analysis. This is because the temporal shape of the predicted response differs between the event-related and the epoch model, with the former reaching its peak sooner and returning to baseline later than the latter. We present data from a blocked design fMRI study of single word reading alternated with rest. Conventionally, such a design would be analyzed using an epoch analysis with boxcar regressors. However, here we used a combined model in which trials were modeled as both single events and epochs. This allowed us to estimate the variance in the BOLD signal that was explained by either the event-related or the epoch regressors having discounted the effect of the other. We found that, in a number of language regions, the event-related model explained changes in activity that were not accounted for by the epoch model. In addition, we show that the advantage of the event-related over epoch model was engendered by its early onset rather than its late offset, relative to the epoch model.

Adult↗

PubMed2003

Estimating efficiency a priori: a comparison of blocked and randomized designs.

This technical note deals with a priori estimation of efficiency of functional magnetic resonance imaging (fMRI) designs. The efficiency of an estimator is a measure of how reliable it is and depends on error variance (the variance not modeled by explanatory variables in the design matrix) and the design variance (a function of the explanatory variables and the contrast tested). Changes in the experimental design can induce changes in the variance of estimated responses. This translates into changes in the standard error of the response estimate or equivalently into changes in efficiency. One consequence is that statistics, testing for the same activation in different contexts (i.e., experimental designs), can change substantially even if the activation and error variance are exactly the same. We demonstrate this effect using an event-related fMRI study of single word reading during blocked and randomized trial presentations. Furthermore, we show that the error variance can change with the experimental design. This highlights a problem with a priori comparison of efficiency for two or more experimental designs, which usually assumes identical error variance.

Adult↗

PubMed2003

The myth of the visual word form area.

Recent functional imaging studies have referred to a posterior region of the left midfusiform gyrus as the "visual word form area" (VWFA). We review the evidence for this claim and argue that neither the neuropsychological nor neuroimaging data are consistent with a cortical region specialized for visual word form representations. Specifically, there are no reported cases of pure alexia who have deficits limited to visual word form processing and damage limited to the left midfusiform. In addition, we present functional imaging data to demonstrate that the so-called VWFA is activated by normal subjects during tasks that do not engage visual word form processing such as naming colors, naming pictures, reading Braille, repeating auditory words, and making manual action responses to pictures of meaningless objects. If the midfusiform region has a single function that underlies all these tasks, then it does not correspond to visual word form processing. On the other hand, if the region participates in several functions as defined by its interactions with other cortical areas, then identifying the neural system sustaining visual word form representations requires identification of the set of regions involved. We conclude that there is no evidence that visual word form representations are subtended by a single patch of neuronal cortex and it is misleading to label the left midfusiform region as the visual word form area.

Cognition↗

PubMed2002

Are subitizing and counting implemented as separate or functionally overlapping processes?

Enumeration of small groups of four or fewer objects is very fast and accurate (often called "subitizing"), but gets slower and more error prone for more than four items ("counting"). Many theories have been proposed to account for this dichotomy, most suggesting that "subitizing" and "counting" are two qualitatively different and separable processes. Others, in contrast, have proposed that the two operations reflect two different levels along a continuum of complexity. In this paper we present a PET study that attempts to characterize subitizing and counting at a neural level in order to investigate whether they are implemented as separate or functionally overlapping processes. Subjects performed an enumeration task on visual arrays of dots that varied in numerosity (1-4 and 6-9 dots) and spatial arrangement (canonical and random). The results demonstrated a common network for subitizing and counting that comprises extrastriate middle occipital and intraparietal areas. The intensity and spatial extent of this network were modulated by the number of dots and their spatial arrangement: activation increased as the number of items in the visual array increased, reaching maximum peak and extent for counting 6-9 randomly arranged items. Direct comparison between subitizing and counting showed that counting, relative to subitizing, was correlated with increased activity in this occipitoparietal network, while subitizing did not show areas of increased activation with respect to counting. Results speak against the idea of the two processes being implemented in separable neural systems.

Adult↗

PubMed2002

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

This article is about intersubject variability in the functional integration of activity in different brain regions. Previous studies of functional and effective connectivity have dealt with intersubject variability by analyzing data from different subjects separately or pretending the data came from the same subject. These approaches do not allow one to test for differences among subjects. The aim of this work was to illustrate how differences in connectivity among subjects can be addressed explicitly using structural equation modeling. This is enabled by constructing a multisubject network that comprises m regions of interest for each of the n subjects studied, resulting in a total of m x n nodes. Constructing a network of regions from different subjects may seem counterintuitive but embodies two key advantages. First, it allows one to test directly for differences among subjects by comparing models that do and do not allow a particular connectivity parameter to vary over subjects. Second, a multisubject network provides additional degrees of freedom to estimate the model's free parameters. Any neurobiological hypothesis normally addressed by single-subject or group analyses can still be tested, but with greater sensitivity. The common influence of experimental variables is modeled by connecting a virtual node, whose time course reflects stimulus onsets, to the sensory or "input" region in all subjects. Further experimental changes in task or cognitive set enter through modulation of the connections. This approach allows one to model both endogenous (or intrinsic) variance and exogenous effects induced by experimental design. We present a functional magnetic resonance imaging study that uses a multisubject network to investigate intersubject variability in functional integration in the context of single word and pseudoword reading. We tested whether the effect of word type on the reading-related coupling differed significantly among subjects. Our results showed that a number of forward and backward connections were stronger for reading pseudowords than words, and, in one case, connectivity showed significant intersubject variability. The discussion focuses on the implications of our findings and on further applications of the multisubject network analysis.

Adult↗

PubMed2002

The importance of distributed sampling in blocked functional magnetic resonance imaging designs.

In this study we demonstrate the importance of distributed sampling of peristimulus time in blocked design fMRI studies. Distributed sampling ensures all the components of an event-related hemodynamic response are sampled and avoids the bias incurred when stimulus presentation is time-locked to data acquisition. We found that differences in the temporal offset between stimulus presentation and data acquisition had a significant effect on some language-related activations. These effects, induced by simply shifting stimulus presentation by a fraction of the interscan interval, suggest that fixed sampling does indeed bias estimated responses, even in blocked designs.

Adult↗

PubMed2002

Is there an anatomical basis for category-specificity? Semantic memory studies in PET and fMRI.

Patients with semantic impairments sometimes demonstrate category-specific deficits suggesting that the anatomical substrates of semantic memory may reflect categorical organisation, however, neuroimaging studies have failed to provide consistent data in support of a category-based account. We conducted three functional neuroimaging experiments to investigate the neural correlates of semantic processing, two with positron emission tomography (PET) and a third with functional magnetic resonance imaging (fMRI). The first experiment used a lexical decision task to search for brain regions selectively activated by concepts from four different categories--animals, fruit, tools, and vehicles. The second experiment used a semantic categorisation task to increase the demands on the semantic system and to look for evidence of consistent activations for the domains of natural kinds or man-made items. The final experiment was a replication of the semantic categorisation task using fMRI to increase the spatial resolution and statistical sensitivity of the experiment. The results of these experiments reliably identified a distributed neural system common to both natural kinds and artifacts but failed to find robust evidence of functional segregation by domain or categories. Category effects were neither reliable nor consistently present across experiments although some were consistent with previous studies. We discuss the implications of these findings, arguing that they are most consistent with a semantic system undifferentiated by category at the neural level.

Adult↗

PubMed2002

Functional imaging studies of neuropsychological patients: applications and limitations.

Functional imaging studies of neuropsychologically impaired patients have not enjoyed the immediate success that was attained by functional imaging studies of normal subjects. This is largely because it has taken time to appreciate some of the deeper issues surrounding study design, analysis and interpretation. The most significant limitation is that functional imaging experiments with patients need tasks that the patients can perform. This precludes direct investigations of the physiological correlates of cognitive deficits. Nevertheless, functional imaging studies of brain-damaged patients who retain task competence can provide information that is not available from structural imaging, behavioural assessments or functional imaging with normal subjects. This is because intact task performance, following a brain lesion, does not necessarily entail normal neuronal responses in undamaged cortical areas. Abnormal neuronal responses, in the context of normal performance, can indicate alternative neuronal and cognitive mechanisms for supporting the same task. This, in turn, has important implications for understanding the mechanisms that mediate recovery and the organizational principles that underlie functional architectures in the human brain.

Brain Damage, Chronic↗

PubMed2002

Can segregation within the semantic system account for category-specific deficits?

Functional neuroimaging was used to investigate the extent to which category-specific semantic deficits in patients can be accounted for in terms of the demands placed on neural systems underlying different types of semantic knowledge. Unlike previous functional imaging studies of category specificity, we used a factorial design that crossed category (tools and fruits) with tasks requiring retrieval of either action or perceptual (real life size) knowledge. The presentation of tools relative to fruit increased activation in the same left posterior middle temporal area that was linked to the retrieval of action knowledge in general (for fruit as well as tools). However, we found no correlation between activation evoked by fruit and the size retrieval task. The left medial anterior temporal cortex was the only region to be activated for fruit relative to tools. We argue that the sensory-functional theory of category-specific effects is insufficient to account for the current neuroimaging literature. However, the data do support a more refined version of the theory: tools, relative to fruit, are more strongly linked to manipulative/motor knowledge and, for some tasks, fruit may be more reliant on integrating multiple semantic features.

Adult↗