Brain abnormalities underlying altered activation in dyslexia: a voxel based morphometry study.

Voxel-based morphometry was used to assess the consistency among functional imaging and brain morphometry data in developmental dyslexia. Subjects, from three different cultural contexts (UK, France and Italy), were the same as those described in a previous PET activation paper, which revealed a common pattern of reduced activation during reading tasks in the left temporal and occipital lobes. We provide evidence that altered activation observed within the reading system is associated with altered density of grey and white matter of specific brain regions, such as the left middle and inferior temporal gyri and the left arcuate fasciculus. This supports the view that dyslexia is associated with both local grey matter dysfunction and with altered connectivity among phonological/reading areas. The differences were replicable across samples confirming that the neurological disorder underlying dyslexia is the same across the cultures investigated in the study.

Thinking about intentions.

In this fMRI study, we investigated the convergence of underlying neural networks in thinking about a scenario involving one's own intentional action and its consequences and setting up and holding in mind an intention to act. A factorial design was employed comprising two factors: i. Causality (intentional or physical events) and ii. Prospective Memory (present or absent). In each condition, subjects answered questions about various hypothetical scenarios, which related either to the link between the subject's own intentions and consequential actions (Intentional Causality) or to the link between a natural, physical event and its consequences (Physical Causality). A prospective memory task was embedded in half the blocks. In this task, subjects were required to keep in mind an intention (to press a key on seeing a red stimulus background) whilst carrying out the ongoing Causality task. Answering questions about intentional causality versus physical causality activated a network of regions that have traditionally been associated with Theory of Mind, including the medial prefrontal cortex (mPFC), the superior temporal sulcus and the temporal poles bilaterally. In addition, the precuneus bordering with posterior cingulate cortex, an area involved in self-awareness and self-related processing, was activated more when thinking about intentional causality. In the prospective memory task, activations were found in the right parietal cortex, frontopolar cortex (BA 10) and precuneus. Different subregions within the precuneus/posterior cingulate cortex were activated in both main effects of intentional causality and prospective memory. Therefore, the precuneus/posterior cingulate cortex subserves separately thinking about one's own intentions and consequent actions and bearing in mind an intention to make an action. Previous studies have shown that prospective memory, requiring the formation of an intention and the execution of a corresponding action, is associated with decreased activation in the dorsal mPFC, close to the region activated in Theory of Mind tasks. Here, we found that holding in mind an intention to act and at the same time thinking about an intentional action led to reduced activity in a dorsal section of the mPFC. This was a different region from a more anterior, inferior dorsal mPFC region that responded to intentional causality. This suggests that different regions of mPFC play different roles in thinking about intentions.

Fractionation of visual memory: agency detection and its impairment in autism.

It is known that the adult visual memory system is fractionable into functionally independent cognitive subsystems, selectively susceptible to brain damage. In addition, there have been hints from studies with individuals with autism that these cognitive subsystems can fractionate developmentally. However, there has been a paucity of systematic investigations. The present study involves the analysis of visual memory of a population of individuals with autism and age- and VIQ-matched comparison individuals. The individuals with autism presented selective impairments in face recognition in comparison to both the age- and VIQ-matched comparison populations. In addition, they were impaired relative to the age-matched comparison group on recognition memory for potential agents (i.e. objects capable of self-propelled motion) whether they were living (cats and horses) or non-living (motorbikes). In contrast, they were selectively superior relative to the VIQ-matched comparison group on recognition memory for such objects as topographical stimuli (buildings) and leaves that clearly do not have agency. The data is interpreted in terms of reduced sensitivity to agency cues in individuals with autism and general information processing capacity.

Reward value of attractiveness and gaze.

Faces are visual objects in our environment that provide strong social cues, with the eyes assuming particular importance. Here we show that the perceived attractiveness of an unfamiliar face increases brain activity in the ventral striatum of the viewer when meeting the person's eye, and decreases activity when eye gaze is directed away. Depending on the direction of gaze, attractiveness can thus activate dopaminergic regions that are strongly linked to reward prediction, indicating that central reward systems may be engaged during the initiation of social interactions.

Are there sex differences in the brain basis of literacy related skills? Evidence from reading and spelling impairments after early unilateral brain damage.

Reading and spelling performance was analysed for a sample of 45 children with unilateral brain damage. Boys showed impairments only when the lesion was on the left, while girls showed no significant impairments when either hemisphere was affected. The results support the hypothesis that specialised substrates, which underlie literacy acquisition, have limited plasticity and may be more strongly lateralised to the left hemisphere in males than in females.

Exploring the cognitive phenotype of autism: weak "central coherence" in parents and siblings of children with autism: I. Experimental tests.

Previous twin and family studies have indicated that there are strong genetic influences in the etiology of autism, and provide support for the notion of a broader phenotype in first-degree relatives. The present study explored this phenotype in terms of one current cognitive theory of autism. Parents and brothers of boys with autism, boys with dyslexia, and normal boys were given tests of "central coherence", on which children with autism perform unusually well due to an information-processing bias favouring part/detail processing over processing of wholes/meaning. Results indicated that fathers of boys with autism, as a group, showed piecemeal processing across four tests of central coherence. This was not true for any other group. These findings raise the possibility that the broader autism phenotype may include a "cognitive style" (weak central coherence) that can confer information-processing advantages.

Exploring the cognitive phenotype of autism: weak "central coherence" in parents and siblings of children with autism: II. Real-life skills and preferences.

Information on everyday life activities and preferences in both social and nonsocial domains was obtained from parents and children who had taken part in an experimental study of central coherence. Comparisons were made between parents who had a son with autism, parents with a dyslexic son, and families without a history of developmental disorder, as well as the male siblings in these families. Data on everyday preferences and abilities were elicited by means of an experimental questionnaire. Significant group differences in social and nonsocial preferences were found, suggesting that some parents showed similarities with their son with autism, in preference for nonsocial activities and ability in detail-focused processing. A similar experimental questionnaire, completed by parents on behalf of their sons, discriminated between autism group probands and controls, but did not differentiate sibling groups. The relevance of the nonsocial items to central coherence is discussed in the light of the findings in Part I: autism parents who reported more autism-related nonsocial (but not social) preferences, tended to show a piecemeal processing style on the experimental tasks.

Dyslexia: cultural diversity and biological unity.

The recognition of dyslexia as a neurodevelopmental disorder has been hampered by the belief that it is not a specific diagnostic entity because it has variable and culture-specific manifestations. In line with this belief, we found that Italian dyslexics, using a shallow orthography which facilitates reading, performed better on reading tasks than did English and French dyslexics. However, all dyslexics were equally impaired relative to their controls on reading and phonological tasks. Positron emission tomography scans during explicit and implicit reading showed the same reduced activity in a region of the left hemisphere in dyslexics from all three countries, with the maximum peak in the middle temporal gyrus and additional peaks in the inferior and superior temporal gyri and middle occipital gyrus. We conclude that there is a universal neurocognitive basis for dyslexia and that differences in reading performance among dyslexics of different countries are due to different orthographies.

TMS produces two dissociable types of speech disruption.

We aimed to use repetitive transcranial magnetic stimulation (rTMS) to disrupt speech with the specific objective of dissociating speech disruption according to whether or not it was associated with activation of the mentalis muscle. Repetitive transcranial magnetic stimulation (rTMS) was applied over two sites of the right and left hemisphere while subjects counted aloud and recited the days of the week, months of the year, and nursery rhymes. Analysis of EMG data and videotaped recordings showed that rTMS applied over a posterior site, lateral to the motor hand area of both the right and the left hemisphere resulted in speech disruption that was accompanied by activation of the mentalis muscle, while rTMS applied over an anterior site on the left but not the right hemisphere resulted in speech disruption that was dissociated from activation of the mentalis muscle. The findings provide a basis for the use of subthreshold stimulation over the extrarolandic speech disruption site in order to probe the functional properties of this area and to test psychological theories of linguistic function.

What framework should we use for understanding developmental disorders?

The neuropsychology of dyslexia has made great strides in the last decade. In particular, a consensus views dyslexia as a developmental disorder with a basis in the brain and in the genes, where the interaction of genetic and environmental factors is taken for granted. However, problems in defining the phenotype continue to bedevil research. The main conceptual problems can be expressed in three main questions: (a) Is dyslexia based on a specific brain abnormality or is it merely part of a continuum of atypical brain development? (b) When can we speak of comorbidity? (c) Why does so much individual variability occur? These questions can be tackled in a common framework that takes into account simultaneously three levels: the biological, the cognitive, and the behavioral.

Mind blindness and the brain in autism.

Experimental evidence shows that the inability to attribute mental states, such as desires and beliefs, to self and others (mentalizing) explains the social and communication impairments of individuals with autism. Brain imaging studies in normal volunteers highlight a circumscribed network that is active during mentalizing and links medial prefrontal regions with posterior superior temporal sulcus and temporal poles. The brain abnormality that results in mentalizing failure in autism may involve weak connections between components of this system.

Left posterior BA37 is involved in object recognition: a TMS study.

Functional imaging studies have proposed a role for left BA37 in phonological retrieval, semantic processing, face processing and object recognition. The present study targeted the posterior aspect of BA37 to see whether a deficit, specific to one of the above types of processing could be induced. Four conditions were investigated: word and nonword reading, colour naming and picture naming. Repetitive transcranial magnetic stimulation (rTMS) was delivered over posterior BA37 of the left and right hemispheres (lBA37 and rBA37, respectively) and over the vertex. Subjects were significantly slower to name pictures when TMS was given over lBA37 compared to vertex or rBA37. rTMS over lBA37 had no significant effect on word reading, nonword reading or colour naming. The picture naming deficit is suggested to result from a disruption to object recognition processes. This study corroborates the finding from a recent imaging study, that the most posterior part of left hemispheric BA37 has a necessary role in object recognition.

Abnormal functional activation during a simple word repetition task: A PET study of adult dyslexics.

Eight dyslexic subjects, impaired on a range of tasks requiring phonological processing, were matched for age and general ability with six control subjects. Participants were scanned using positron emission tomography (PET) during three conditions: repeating real words, repeating pseudowords, and rest. In both groups, speech repetition relative to rest elicited widespread bilateral activation in areas associated with auditory processing of speech; there were no significant differences between words and pseudowords. However, irrespective of word type, the dyslexic group showed less activation than the control group in the right superior temporal and right post-central gyri and also in the left cerebellum. Notably, the right anterior superior temporal cortex (Brodmann's area 22 [BA 22]) was less activated in each of the eight dyslexic subjects, compared to each of the six control subjects. This deficit appears to be specific to auditory repetition as it was not detected in a previous study of reading which used the same sets of stimuli (Brunswick, N., McCrory, E., Price, C., Frith, C.D., & Frith, U. [1999]. Explicit and implicit processing of words and pseudowords by adult developmental dyslexics: A search for Wernicke's Wortschatz? Brain, 122, 1901-1917). This implies that the observed neural manifestation of developmental dyslexia is task-specific (i.e., functional rather than structural). Other studies of normal subjects indicate that attending to the phonetic structure of speech leads to a decrease in right-hemisphere processing. Lower right hemisphere activation in the dyslexic group may therefore indicate less processing of non-phonetic aspects of speech, allowing greater salience to be accorded to phonological aspects of attended speech.

Movement and mind: a functional imaging study of perception and interpretation of complex intentional movement patterns.

We report a functional neuroimaging study with positron emission tomography (PET) in which six healthy adult volunteers were scanned while watching silent computer-presented animations. The characters in the animations were simple geometrical shapes whose movement patterns selectively evoked mental state attribution or simple action description. Results showed increased activation in association with mental state attribution in four main regions: medial prefrontal cortex, temporoparietal junction (superior temporal sulcus), basal temporal regions (fusiform gyrus and temporal poles adjacent to the amygdala), and extrastriate cortex (occipital gyrus). Previous imaging studies have implicated these regions in self-monitoring, in the perception of biological motion, and in the attribution of mental states using verbal stimuli or visual depictions of the human form. We suggest that these regions form a network for processing information about intentions, and speculate that the ability to make inferences about other people's mental states evolved from the ability to make inferences about other creatures' actions.

High "intelligence," low "IQ"? Speed of processing and measured IQ in children with autism.

The uneven profile of performance on standard assessments of intelligence and the high incidence of savant skills have prompted interest in the nature of intelligence in autism. The present paper reports the first group study of speed of processing in children with autism (IQ 1 SD below average) using an inspection time task. The children with autism showed inspection times as fast as an age-matched group of young normally developing children (IQ 1 SD above average). They were also significantly faster than mentally handicapped children without autism of the same age, even when these groups were pairwise matched on Wechsler IQ. To the extent that IT tasks tap individual differences in basic processing efficiency, children with autism in this study appear to have preserved information processing capacity despite poor measured IQ. These findings have implications for the role of general and specific cognitive systems in knowledge and skill acquisition: far from showing that children with autism are unimpaired, we suggest that our data may demonstrate the vital role of social insight in the development of manifest "intelligence."

Precursors of literacy delay among children at genetic risk of dyslexia.

This paper reports the literacy skills of 63 children selected as being at genetic risk of dyslexia compared with 34 children from families reporting no history of reading impairment. Fifty-seven per cent of the at-risk group were delayed in literacy development at 6 years compared with only 12% of controls. The "unimpaired" at-risk group were not statistically different from controls on most cognitive and language measures at 45 months, whereas the literacy-delayed group showed significantly slower speech and language development, although they did not differ from controls in nonverbal ability. Letter knowledge at 45 months was the strongest predictor of literacy level at 6 years. In addition, early speech and language skills predicted individual differences in literacy outcome and genetic risk accounted for unique variance over and above these other factors. The results are discussed in terms of an interactive developmental model in which semantic and phonological skills support early reading acquisition.

Reading the mind in cartoons and stories: an fMRI study of 'theory of mind' in verbal and nonverbal tasks.

Previous functional imaging studies have explored the brain regions activated by tasks requiring 'theory of mind'--the attribution of mental states. Tasks used have been primarily verbal, and it has been unclear to what extent different results have reflected different tasks, scanning techniques, or genuinely distinct regions of activation. Here we report results from a functional magnetic resonance imaging study (fMRI) involving two rather different tasks both designed to tap theory of mind. Brain activation during the theory of mind condition of a story task and a cartoon task showed considerable overlap, specifically in the medial prefrontal cortex (paracingulate cortex). These results are discussed in relation to the cognitive mechanisms underpinning our everyday ability to 'mind-read'.

A cultural effect on brain function.

We present behavioral and anatomical evidence for a multi-component reading system in which different components are differentially weighted depending on culture-specific demands of orthography. Italian orthography is consistent, enabling reliable conversion of graphemes to phonemes to yield correct pronunciation of the word. English orthography is inconsistent, complicating mapping of letters to word sounds. In behavioral studies, Italian students showed faster word and non-word reading than English students. In two PET studies, Italians showed greater activation in left superior temporal regions associated with phoneme processing. In contrast, English readers showed greater activations, particularly for non-words, in left posterior inferior temporal gyrus and anterior inferior frontal gyrus, areas associated with word retrieval during both reading and naming tasks.