Biomedical subjects

Andrea Mechelli

Publications and source records attributed to Andrea Mechelli.

At least 19 recordsLinked to original sources

PubMed2007

Dissociating stimulus-driven semantic and phonological effect during reading and naming.

The aim of the present study was to dissociate the neural correlates of semantic and phonological processes during word reading and picture naming. Previous studies have addressed this issue by contrasting tasks involving semantic and phonological decisions. However, these tasks engage verbal short-term memory and executive functions that are not required for reading and naming. Here, 20 subjects were instructed to overtly name written words and pictures of objects while their neuronal responses were measured using functional magnetic resonance imaging (fMRI). Each trial consisted of a pair of successive stimuli that were either semantically related (e.g., "ROBIN-nest"), phonologically related (e.g., "BELL-belt"), unrelated (e.g., "KITE-lobster"), or semantically and phonologically identical (e.g., "FRIDGE-fridge"). In addition, a pair of stimuli could be presented in either the same modality (word-word or picture-picture) or a different modality (word-picture or picture-word). We report that semantically related pairs modulate neuronal responses in a left-lateralized network, including the pars orbitalis of the inferior frontal gyrus, the middle temporal gyrus, the angular gyrus, and the superior frontal gyrus. We propose that these areas are involved in stimulus-driven semantic processes. In contrast, phonologically related pairs modulate neuronal responses in bilateral insula. This region is therefore implicated in the discrimination of similar, competing phonological and articulatory codes. The above effects were detected with both words and pictures and did not differ between the two modalities even with a less conservative statistical threshold. In conclusion, this study dissociates the effects of semantic and phonological relatedness between successive items during reading and naming aloud.

Adolescent↗

PubMed2006

Exact and approximate judgements of visual and auditory numerosity: an fMRI study.

Human adults can assess the number of objects in a set (numerosity) by approximate estimation or by exact counting. There is evidence suggesting that numerosity estimation depends on a dedicated mechanism that is a-modal and non-verbal. By contrast, counting requires the coordination between the pre-existing numerosity estimation abilities with language and one-to-one correspondence principles. In this paper we investigate with fMRI the neural correlates of numerosity estimation and counting in human adults, using both visual and auditory stimuli. Results show that attending to approximate numerosity correlates with increased activity of a right lateralized fronto-parietal cortical network, and that this activity is independent of the stimuli presentation's modality. Counting activates additional left prefrontal, parietal, and bilateral premotor areas, again independently from stimulus modality. These results dissociate two neuronal systems that underlie different numerosity judgements.

Acoustic Stimulation↗

PubMed2006

Effect of word and syllable frequency on activation during lexical decision and reading aloud.

This functional MRI (fMRI) study investigated the effect of lexical and syllable frequency on visual word processing during lexical decision and reading aloud. Previous research has shown a dissociation of syllable and word frequency effects in Spanish using behavioral and electrophysiological measures, suggesting that sublexical (syllabic) representations are computed and mediate the firing of lexical candidates. Here, we characterize the neuroanatomical basis of these lexical and sublexical manipulations and their dependence on task. During lexical decision, words with low vs. high lexical frequency increased activation in left frontal, anterior cingulate, supplemental motor area (SMA), and pre-SMA regions; while words with high vs. low syllable frequency increased activation in a left anterior inferior temporal region. In contrast, when the words were read aloud those with low vs. high syllable frequency increased activation in the left anterior insula, with no other significant effects. On the basis of the neuroanatomy, we propose that the contrasting effects of syllable frequency during lexical decision and reading aloud reflect two different cognitive processes in visual word processing. Specifically, words with high-frequency syllables may increase lexical competition in the inferior temporal lobe while facilitating articulatory planning in the left anterior insula.

Adult↗

PubMed2005

Semantic relevance explains category effects in medial fusiform gyri.

We used functional Magnetic Resonance Imaging to explore the neural correlates of semantic relevance in 12 healthy participants performing a picture-naming task. In addition, we tested the hypothesis that category effects typically found in functional imaging can be partly explained in terms of different semantic relevance for animals and artefacts. We report that semantic relevance modulates neuronal responses in the medial fusiform gyrus bilaterally. As predicted, category effects in this region are strongly modulated by the semantic relevance of the items. Specifically, the effect of artefacts > animals is greatly reduced when the two categories are matched for semantic relevance. Thus, the present study demonstrates that neuronal responses during concept retrieval are modulated by the semantic relevance of the features. It also suggests that increased activation in the medial fusiform gyrus typically found for artefacts > animals can be explained by different semantic relevance for animal and artefact items.

Adult↗

PubMed2005

Structural covariance in the human cortex.

The morphology of the human cortex varies remarkably across individuals, regardless of overall brain size. It is currently unclear whether related cortical regions covary in gray matter density, as a result of mutually trophic influences or common experience-related plasticity. We acquired a structural magnetic resonance imaging scan from 172 subjects and extracted the regional gray matter densities from 12 readily identifiable regions of interest involved in sensorimotor or higher-order cognitive functions. We then used these values to predict regional densities in the remaining areas of the cortex, using voxel-based morphometry. This revealed patterns of positive and negative covariance that provide insight into the topographical organization of multiple cortical regions. We report that the gray matter density of a region is a good predictor of the density of the homotopic region in the contralateral hemisphere, with the striking exception of primary visual cortex. Whereas some regions express patterns of regional covariance that are mirror symmetrical relative to the interhemispheric fissure, other regions express asymmetric patterns of regional covariance. Finally, patterns of covariance are remarkably consistent between males and females, with the exception of the left amygdala, which is positively associated with the left and right anterior inferior temporal cortex in males and with the right angular gyrus in females. Our study establishes that the density of different cortical regions is coordinated within an individual. The coordinated variations we report are likely to be determined by both genetic and environmental factors and may be the basis for differences in individual behavior.

Adult↗

PubMed2005

Reading and reading disturbance.

Recent functional neuroimaging studies are generating novel insights into our knowledge of skilled and disturbed reading. In neurologically normal subjects, a double dissociation in neural activation in response to reading words and pseudowords has been revealed that corresponds to that observed in the comparison of semantic and phonological tasks. In patients with acquired dyslexia, functional imaging is demonstrating re-organisation within the reading system; in developmental dyslexia, functional imaging is being used to identify the impact of rehabilitation. Together, these findings have implications for cognitive models of reading that have previously relied on input from behavioural data.

Dyslexia↗

PubMed2005

Fusiform activation to animals is driven by the process, not the stimulus.

Previous studies have found that the lateral posterior fusiform gyri respond more robustly to pictures of animals than pictures of manmade objects and suggested that these regions encode the visual properties characteristic of animals. We suggest that such effects actually reflect processing demands arising when items with similar representations must be finely discriminated. In a positron emission tomography (PET) study of category verification with colored photographs of animals and vehicles, there was robust animal-specific activation in the lateral posterior fusiform gyri when stimuli were categorized at an intermediate level of specificity (e.g., dog or car). However, when the same photographs were categorized at a more specific level (e.g., Labrador or BMW), these regions responded equally strongly to animals and vehicles. We conclude that the lateral posterior fusiform does not encode domain-specific representations of animals or visual properties characteristic of animals. Instead, these regions are strongly activated whenever an item must be discriminated from many close visual or semantic competitors. Apparent category effects arise because, at an intermediate level of specificity, animals have more visual and semantic competitors than do artifacts.

Adult↗

PubMed2005

Dissociating reading processes on the basis of neuronal interactions.

Previous studies of patients with phonological and surface alexia have demonstrated a double dissociation between the reading of pseudo words and words with atypical spelling-to-sound relationships. A corresponding double dissociation in the neuronal activation patterns for pseudo words and exception words has not, however, been consistently demonstrated in normal subjects. Motivated by the literature on acquired alexia, the present study contrasted pseudo words to exception words and explored how neuronal interactions within the reading system are influenced by word type. Functional magnetic resonance imaging was used to measure neuronal responses during reading in 22 healthy volunteers. The direct comparison of reading pseudo words and exception words revealed a double dissociation within the left frontal cortex. Pseudo words preferentially increased left dorsal premotor activation, whereas exception words preferentially increased left pars triangularis activation. Critically, these areas correspond to those previously associated with phonological and semantic processing, respectively. Word-type dependent interactions between brain areas were then investigated using dynamic causal modeling. This revealed that increased activation in the dorsal premotor cortex for pseudo words was associated with a selective increase in effective connectivity from the posterior fusiform gyrus. In contrast, increased activation in the pars triangularis for exception words was associated with a selective increase in effective connectivity from the anterior fusiform gyrus. The present investigation is the first to identify distinct neuronal mechanisms for semantic and phonological contributions to reading.

Adult↗

PubMed2004

More than words: a common neural basis for reading and naming deficits in developmental dyslexia?

Dyslexic individuals show subtle impairments in naming pictures of objects in addition to their difficulties with reading. The present study investigated whether word reading and picture naming deficits in developmental dyslexia can be reduced to a common neurological impairment. Eight dyslexic subjects, impaired on measures of reading, spelling and naming speed, were matched for age and general ability with 10 control subjects. Participants were scanned using PET during two experimental conditions: reading words and naming pictures in the form of corresponding line drawings. In addition, two high-level baseline conditions were used to control for visual and articulatory processes. Relative to the control group, the dyslexic participants showed reduced activation in a left occipitotemporal area during both word reading and picture naming. This was the case even in the context of intact behavioural performance during scanning. Abnormal activation in this region, as reported previously for reading, is therefore not specific to orthographic decoding but may reflect a more general impairment in integrating phonology and visual information. Our investigation points to a common neurological basis for deficits in word reading and picture naming in developmental dyslexia.

Adolescent↗

PubMed2004

Neurolinguistics: structural plasticity in the bilingual brain.

Humans have a unique ability to learn more than one language--a skill that is thought to be mediated by functional (rather than structural) plastic changes in the brain. Here we show that learning a second language increases the density of grey matter in the left inferior parietal cortex and that the degree of structural reorganization in this region is modulated by the proficiency attained and the age at acquisition. This relation between grey-matter density and performance may represent a general principle of brain organization.

Age Factors↗

PubMed2004

Where bottom-up meets top-down: neuronal interactions during perception and imagery.

Functional magnetic resonance imaging (fMRI) studies have identified category-selective regions in ventral occipito-temporal cortex that respond preferentially to faces and other objects. The extent to which these patterns of activation are modulated by bottom-up or top-down mechanisms is currently unknown. We combined fMRI and dynamic causal modelling to investigate neuronal interactions between occipito-temporal, parietal and frontal regions, during visual perception and visual imagery of faces, houses and chairs. Our results indicate that, during visual perception, category-selective patterns of activation in extrastriate cortex are mediated by content-sensitive forward connections from early visual areas. In contrast, during visual imagery, category-selective activation is mediated by content-sensitive backward connections from prefrontal cortex. Additionally, we report content-unrelated connectivity between parietal cortex and the category-selective regions, during both perception and imagery. Thus, our investigation revealed that neuronal interactions between occipito-temporal, parietal and frontal regions are task- and stimulus-dependent. Sensory representations of faces and objects are mediated by bottom-up mechanisms arising in early visual areas and top-down mechanisms arising in prefrontal cortex, during perception and imagery respectively. Additionally non-selective, top-down processes, originating in superior parietal areas, contribute to the generation of mental images, regardless of their content, and their maintenance in the 'mind's eye'.

Adult↗

PubMed2003

A dynamic causal modeling study on category effects: bottom-up or top-down mediation?

In this study, we combined functional magnetic resonance imaging (fMRI) and dynamic causal modeling (DCM) to investigate whether object category effects in the occipital anti temporal cortex are mediated by inputs from early visual cortex or parietal regions. Resolving this issue may provide anatomical constraints on theories of category specificity--which make different assumptions about the underlying neurophysiology. The data were acquired by Ishai, Ungerleider, Martin, Schouten, and Haxby (1999, 2000) and provided by the National fiNRI Data Center (http://www.fmridcc.org). The original authors used a conventional analysis to estimate differential effects in the occipital anti temporal cortex in response to pictures of chairs, faces, and houses. We extended this approach by estimating neuronal interactions that mediate category effects using DCM. DCM uses a Bayesian framework to estimate and make inferences about the influence that one region exerts over another and how this is affected by experimental changes. DCM differs from previous approaches to brain connectivity, such as multivariate autoregressive models and structural equation modeling, as it assumes that the observed hemodynamic responses are driven by experimental changes rather than endogenous noise. DCM therefore brings the analysis of brain connectivity much closer to the analysis of regionally specific effects usually applied to functional imaging data. We used DCM to estimate the influence that V3 and the superior/inferior parietal cortex exerted over category-responsive regions and how this was affected by the presentation of houses, faces, and chairs. We found that category effects in occipital and temporal cortex were mediated by inputs from early visual cortex. In contrast,the connectivity from the superior/inferior parietal area to the category-responsive areas was unaffected by the presentation of chairs, faces, or houses. These findings indicate that category effects in the occipital and temporal cortex can be mediated by bottom-up mechanisms-a finding that needs to be embraced by models of category specificity.

Brain↗

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

Normal and pathological reading: converging data from lesion and imaging studies.

In this paper we discuss cognitive and anatomical models of reading that have emerged from behavioral and lesion studies of dyslexia and functional neuroimaging studies of normal subjects. We then suggest that discrepancies in their findings can partly be overcome by functional neuroimaging studies of patients with acquired dyslexia. We present two such studies. One patient had a large left temporoparietal lesion which limited his reading to words with high semantic associations. When he read these words aloud, activation was observed in all areas of the normal reading system with the exception of the damaged left superior temporal lobe. The second patient had anterior temporal lobe atrophy with semantic dementia and a deficit in reading words that rely on lexical or semantic mediation. When asked to read aloud words on which she was likely to succeed, she activated all the normal areas, with increased activation in a left sensorimotor area associated with phonological processing and decreased activation in several areas associated with semantic processing. By relating these findings to those from lesion studies and imaging studies of normals, we propose that the translation of orthography to phonology is mediated semantically by the anterior part of the left midfusiform gyrus. In contrast, when semantic processing is compromised, the translation of orthography to phonology will be more reliant on the posterior part of the left midfusiform and the left frontal areas associated with phonology. Future studies are required to examine the connectivity between these areas during normal and abnormal reading.

Brain↗

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

A report of the functional connectivity workshop, Dusseldorf 2002.

This report provides a commentary on the issues presented and discussed at the recent "Functional Brain Connectivity" workshop, held in Dusseldorf, Germany. The workshop brought together researchers using different approaches to study connectivity in the brain, providing them with an opportunity to share conceptual, mathematical, and experimental ideas and to develop strategies and collaborations for future work on functional integration. The main themes that emerged included: (1) the importance of anatomical knowledge in understanding functional interactions the brain; (2) the need to establish common definitions for terms used across disciplines; (3) the need to develop a satisfactory framework for inferring causality from functional imaging and EEG/MEG data; (4) the importance of analytic tools that capture the dynamics of neural interactions; and (5) the role of experimental paradigms that exploit the functional imaging of perturbations to cortical interactions.

Animals↗

PubMed2003

The Functional Brain Connectivity Workshop: report and commentary.

This report summarizes the presentations and discussions at a recent workshop entitled 'Functional Brain Connectivity', held in Düsseldorf, Germany. The aims of the workshop were to bring together researchers using different approaches to study connectivity in the brain, to enable them to share conceptual, mathematical and experimental ideas and to develop strategies for future work on functional integration. The main themes that emerged included: (1) the importance of anatomical knowledge in understanding functional interactions the brain; (2) the need to establish common definitions for terms used across disciplines; (3) the need to develop a satisfactory framework for inferring causality from functional imaging and electroencephalographic/magneto-encephalographic data; (4) the importance of analytic tools that capture the dynamics of neural interactions; and (5) the role of experimental paradigms that exploit the functional imaging of perturbations to cortical interactions.

Animals↗