How do our abilities to process number and other continuous quantities such as time and space relate to each other? Recent evidence suggests that these abilities share common magnitude processing and neural resources, although other findings also highlight the role of dimension-specific processes. To further characterize the relation between number, time, and space, we first examined them in a population with a developmental numerical dysfunction (developmental dyscalculia) and then assessed the extent to which these abilities correlated both behaviorally and anatomically in numerically normal participants. We found that (1) participants with dyscalculia showed preserved continuous quantity processing and (2) in numerically normal adults, numerical and continuous quantity abilities were at least partially dissociated both behaviorally and anatomically. Specifically, gray matter volume correlated with both measures of numerical and continuous quantity processing in the right TPJ; in contrast, individual differences in number proficiency were associated with gray matter volume in number-specific cortical regions in the right parietal lobe. Together, our new converging evidence of selective numerical impairment and of number-specific brain areas at least partially distinct from common magnitude areas suggests that the human brain is equipped with different ways of quantifying the outside world.

Previous studies have demonstrated that the repetition of pseudowords engages a network of premotor areas for articulatory planning and articulation. However, it remains unclear how these premotor areas interact and drive one another during speech production. We used fMRI with dynamic causal modeling to investigate effective connectivity between premotor areas during overt repetition of words and pseudowords presented in both the auditory and visual modalities. Regions involved in phonological aspects of language production were identified as those where regional increases in the BOLD signal were common to repetition in both modalities. We thus obtained three seed regions: the bilateral pre-SMA, left dorsal premotor cortex (PMd), and left ventral premotor cortex that were used to test 63 different models of effective connectivity in the premotor network for pseudoword relative to word repetition. The optimal model was identified with Bayesian model selection and reflected a network with driving input to pre-SMA and an increase in facilitatory drive from pre-SMA to PMd during repetition of pseudowords. The task-specific increase in effective connectivity from pre-SMA to left PMd suggests that the pre-SMA plays a supervisory role in the generation and subsequent sequencing of motor plans. Diffusion tensor imaging-based fiber tracking in another group of healthy volunteers showed that the functional connection between both regions is underpinned by a direct cortico-cortical anatomical connection.

Age has a differential effect on cognition, with word retrieval being one of the cognitive domains most affected by aging. This study examined the functional and structural neural correlates of phonological word retrieval in younger and older adults using word and picture rhyme judgment tasks. Although the behavioral performance in the fMRI task was similar for the two age groups, the older adults had increased activation in the right pars triangularis across tasks and in the right pars orbitalis for the word task only. Increased activation together with preserved performance in the older participants would suggest that increased activation was related to compensatory processing. We validated this hypothesis by showing that right pars triangularis activation during correct rhyme judgments was highest in participants who made overall more errors, therefore being most error-prone. Our findings demonstrate that the effect of aging differ in adjacent but distinct right inferior frontal regions. The differential effect of age on word and picture tasks also provides new clues to the level of processing that is most affected by age in speech production tasks. Specifically, we suggest that right inferior frontal activation in older participants is needed to inhibit errors.

A central feature of auditory STM is its item-limited processing capacity. We investigated whether auditory STM capacity correlated with regional gray and white matter in the structural MRI images from 74 healthy adults, 40 of whom had a prior diagnosis of developmental dyslexia whereas 34 had no history of any cognitive impairment. Using whole-brain statistics, we identified a region in the left posterior STS where gray matter density was positively correlated with forward digit span, backward digit span, and performance on a “spoonerisms” task that required both auditory STM and phoneme manipulation. Across tasks and participant groups, the correlation was highly significant even when variance related to reading and auditory nonword repetition was factored out. Although the dyslexics had poorer phonological skills, the effect of auditory STM capacity in the left STS was the same as in the cognitively normal group. We also illustrate that the anatomical location of this effect is in proximity to a lesion site recently associated with reduced auditory STM capacity in patients with stroke damage. This result, therefore, indicates that gray matter density in the posterior STS predicts auditory STM capacity in the healthy and damaged brain. In conclusion, we suggest that our present findings are consistent with the view that there is an overlap between the mechanisms that support language processing and auditory STM.

Prior lesion and functional imaging studies have highlighted the importance of the left ventral occipito-temporal (LvOT) cortex for visual word recognition. Within this area, there is a posterior–anterior hierarchy of subregions that are specialized for different stages of orthographic processing. The aim of the present fMRI study was to dissociate the effects of subword orthographic typicality (e.g., cider [high] vs. cynic [low]) from the effect of lexicality (e.g., pollen [word] vs. pillen [pseudoword]). We therefore orthogonally manipulated the orthographic typicality of written words and pseudowords (nonwords and pseudohomophones) in a visual lexical decision task. Consistent with previous studies, we identified greater activation for pseudowords than words (i.e., an effect of lexicality) in posterior LvOT cortex. In addition, we revealed higher activation for atypical than typical strings, irrespective of lexicality, in a left inferior occipital region that is posterior to LvOT cortex. When lexical decisions were made more difficult in the context of pseudohomophone foils, left anterior temporal activation also increased for atypical relative to typical strings. The latter finding agrees with the behavior of patients with progressive anterior temporal lobe degeneration, who have particular difficulty recognizing words with atypical orthography. The most novel outcome of this study is that, within a distributed network of regions supporting orthographic processing, we have identified a left inferior occipital region that is particularly sensitive to the typicality of subword orthographic patterns.

Suppressing irrelevant words is essential to successful speech production and is expected to involve general control mechanisms that reduce interference from task-unrelated processing. To investigate the neural mechanisms that suppress visual word interference, we used fMRI and a Stroop task, using a block design with an event-related analysis. Participants indicated with a finger press whether a visual stimulus was colored pink or blue. The stimulus was either the written word “BLUE,” the written word “PINK,” or a string of four Xs, with word interference introduced when the meaning of the word and its color were “incongruent” (e.g., BLUE in pink hue) relative to congruent (e.g., BLUE in blue) or neutral (e.g., XXXX in pink). The participants also made color decisions in the presence of spatial interference rather than word interference (i.e., the Simon task). By blocking incongruent, congruent, and neutral trials, we identified activation related to the mechanisms that suppress interference as that which was greater at the end relative to the start of incongruency. This highlighted the role of the left head of caudate in the control of word interference but not spatial interference. The response in the left head of caudate contrasted to bilateral inferior frontal activation that was greater at the start than at the end of incongruency, and to the dorsal anterior cingulate gyrus which responded to a change in the motor response. Our study therefore provides novel insights into the role of the left head of caudate in the mechanisms that suppress word interference.

Semantically reversible sentences are prone to misinterpretation and take longer for typically developing children and adults to comprehend; they are also particularly problematic for those with language difficulties such as aphasia or Specific Language Impairment. In our study, we used fMRI to compare the processing of semantically reversible and nonreversible sentences in 41 healthy participants to identify how semantic reversibility influences neuronal activation. By including several linguistic and nonlinguistic conditions within our paradigm, we were also able to test whether the processing of semantically reversible sentences places additional load on sentence-specific processing, such as syntactic processing and syntactic-semantic integration, or on phonological working memory. Our results identified increased activation for reversible sentences in a region on the left temporal–parietal boundary, which was also activated when the same group of participants carried out an articulation task which involved saying “one, three” repeatedly. We conclude that the processing of semantically reversible sentences places additional demands on the subarticulation component of phonological working memory.

Using behavioral, structural, and functional imaging techniques, we demonstrate contrasting effects of vocabulary knowledge on temporal and parietal brain structure in 47 healthy volunteers who ranged in age from 7 to 73 years. In the left posterior supramarginal gyrus, vocabulary knowledge was positively correlated with gray matter density in teenagers but not adults. This region was not activated during auditory or visual sentence processing, and activation was unrelated to vocabulary skills. Its gray matter density may reflect the use of an explicit learning strategy that links new words to lexical or conceptual equivalents, as used in formal education and second language acquisition. By contrast, in left posterior temporal regions, gray matter as well as auditory and visual sentence activation correlated with vocabulary knowledge throughout lifespan. We propose that these effects reflect the acquisition of vocabulary through context, when new words are learnt within the context of semantically and syntactically related words.

Neuropsychological and functional imaging studies have associated the conceptual processing of numbers with bilateral parietal regions (including intraparietal sulcus). However, the processes driving these effects remain unclear because both left and right posterior parietal regions are activated by many other conceptual, perceptual, attention, and response-selection processes. To dissociate parietal activation that is number-selective from parietal activation related to other stimulus or response-selection processes, we used fMRI to compare numbers and object names during exactly the same conceptual and perceptual tasks while factoring out activations correlating with response times. We found that right parietal activation was higher for conceptual decisions on numbers relative to the same tasks on object names, even when response time effects were fully factored out. In contrast, left parietal activation for numbers was equally involved in conceptual processing of object names. We suggest that left parietal activation for numbers reflects a range of processes, including the retrieval of learnt facts that are also involved in conceptual decisions on object names. In contrast, number selectivity in right parietal cortex reflects processes that are more involved in conceptual decisions on numbers than object names. Our results generate a new set of hypotheses that have implications for the design of future behavioral and functional imaging studies of patients with left and right parietal damage.

The aim of this study was to find the most prominent source of intersubject variability in neuronal activation for reading familiar words aloud. To this end, we collected functional imaging data from a large sample of subjects ( n = 76) with different demographic characteristics such as handedness, sex, and age, while reading. The subject-by-subject error variance was estimated from a one-sample t test (on all 76 subjects) and was reduced to a lower dimension using principal components decomposition. A Gaussian Mixture Model was then applied to dissociate different subgroups of subjects that explained the main sources of variability in the data. This resulted in the identification of four different subject groups. The comparison of these subgroups to the subjects' demographic details showed that age had a significant effect on the subject partitioning. In addition, a region-by-group dissociation in the dorsal and the ventral inferior frontal cortex was consistent with previously reported dissociations in semantic and nonsemantic reading strategies. In contrast to these significant findings, the groupings did not differentiate subjects on the basis of either sex or handedness, nor did they segregate the subjects with right- versus left-lateralized reading activation. We therefore conclude that, of the variables tested, age and reading strategy were the most prominent source of variability in activation for reading familiar words aloud.

This functional magnetic resonance imaging study compared the neuronal implementation of word and pseudoword processing during two commonly used word recognition tasks: lexical decision and reading aloud. In the lexical decision task, participants made a finger-press response to indicate whether a visually presented letter string is a word or a pseudoword (e.g., “paple”). In the reading-aloud task, participants read aloud visually presented words and pseudowords. The same sets of words and pseudowords were used for both tasks. This enabled us to look for the effects of task (lexical decision vs. reading aloud), lexicality (words vs. nonwords), and the interaction of lexicality with task. We found very similar patterns of activation for lexical decision and reading aloud in areas associated with word recognition and lexical retrieval (e.g., left fusiform gyrus, posterior temporal cortex, pars opercularis, and bilateral insulae), but task differences were observed bilaterally in sensorimotor areas. Lexical decision increased activation in areas associated with decision making and finger tapping (bilateral postcentral gyri, supplementary motor area, and right cerebellum), whereas reading aloud increased activation in areas associated with articulation and hearing the sound of the spoken response (bilateral precentral gyri, superior temporal gyri, and posterior cerebellum). The effect of lexicality (pseudoword vs. words) was also remarkably consistent across tasks. Nevertheless, increased activation for pseudowords relative to words was greater in the left precentral cortex for reading than lexical decision, and greater in the right inferior frontal cortex for lexical decision than reading. We attribute these effects to differences in the demands on speech production and decision-making processes, respectively.

Functional neuroimaging has highlighted a left-hemisphere conceptual system shared by verbal and nonverbal processing despite neuropsychological evidence that the ability to recognize verbal and nonverbal stimuli can doubly dissociate in patients with left- and right-hemisphere lesions, respectively. Previous attempts to control for perceptual differences between verbal and nonverbal stimuli in functional neuroimaging studies may have hidden differences arising at the conceptual level. Here we used a different approach and controlled for perceptual confounds by looking for amodal verbal and nonverbal conceptual activations that are common to both the visual and auditory modalities. In addition to the left-hemisphere conceptual system activated by all meaningful stimuli, we observed the left/right double dissociation in verbal and nonverbal conceptual processing, predicted by neuropsychological studies. Left middle and superior temporal regions were selectively more involved in comprehending words—heard or read—and the right midfusiform and right posterior middle temporal cortex were selectively more involved in making sense of environmental sounds and images. Thus, the neuroanatomical basis of a verbal/nonverbal conceptual processing dissociation is established.

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.

In this study, we combined functional magnetic resonance imaging (fMRI) and dynamic causal modeling (DCM) to investigate whether object category effects in the occipital and 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 fMRI Data Center (http://www.fmridc.org). The original authors used a conventional analysis to estimate differential effects in the occipital and 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.

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.

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.

The effect of stimulus rate and its interaction with stimulus type on brain activity during reading was investigated using functional magnetic resonance imaging (fMRI). This (i) enabled the segregation of brain regions showing differential responses, (ii) identified the optimum experimental design parameters for maximizing sensitivity, and (iii) allowed us to evaluate further the sources of discrepancy between positron emission tomography (PET) and fMRI signals. The effect of visual word rate has already been investigated in a previous PET study. However, rate effects can be very different in PET and fMRI, as seen in previous studies of auditory word processing. In this work, we attempt to replicate rate-sensitive activations observed with PET using fMRI. Our objective was to characterize the discrepancies in regionally specific rate-sensitive effects between the two imaging modalities. Subjects were presented with words and pseudowords at varying rates while performing a silent reading task. The analysis specifically identified regions showing (i) an effect of stimulus rate on brain activity during reading; (ii) modulation of this effect by word type; and (iii) increased activity during reading relative to rest, but with no dependence on stimulus rate. The results identified similar effects of rate for words and pseudowords (no interactions between rate and word type reached significance). Irrespective of word type, strong positive linear effects of rate (i.e., activity increasing with rate) were detected in visual areas, right superior temporal gyrus, and bilateral precentral gyrus. These findings replicate the results of the previous PET study, confirming that activation in regions associated with visual processing and response generation increases with the number of stimuli. Likewise, we detected rate-independent effects reported in the previous PET study in bilateral anterior middle temporal, inferior frontal, and superior parietal regions. These results differentiate the functionally specific responses in rate-dependent and rate-independent areas. However, for negative effects of rate, fMRI did not replicate the effects seen in PET, suggesting some form of hemodynamic “rectification.” The discussion focuses on differences between evoked rCBF and BOLD signals.