Interacting minds--a biological basis.

The ability to "mentalize," that is to understand and manipulate other people's behavior in terms of their mental states, is a major ingredient in successful social interactions. A rudimentary form of this ability may be seen in great apes, but in humans it is developed to a high level. Specific impairments of mentalizing in both developmental and acquired disorders suggest that this ability depends on a dedicated and circumscribed brain system. Functional imaging studies implicate medial prefrontal cortex and posterior superior temporal sulcus (STS) as components of this system. Clues to the specific function of these components in mentalizing come from single cell recording studies: STS is concerned with representing the actions of others through the detection of biological motion; medial prefrontal regions are concerned with explicit representation of states of the self. These observations suggest that the ability to mentalize has evolved from a system for representing actions.

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.

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.

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.

The cognitive basis of a biological disorder: autism.

This article summarizes recent evidence indicating that individuals suffering from autism have a specific problem in understanding intentions and beliefs. We propose that this problem arises because they are incapable of forming a special kind of mental representation. A single cognitive deficit defines what is common to all autistic individuals. In contrast there is a wide range of proposals for the biological origins of the disorder.

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.

The neurocognitive basis of autism.

The cognitive study of the underlying mental abnormalities in autism has advanced rapidly, while the biological study of the underlying brain abnormalities and of putative genetic mechanisms is lagging somewhat behind. However, the linking of cognitive and biological studies has become a real possibility. Developmental cognitive neuroscience has transformed our understanding of this enigmatic disorder, which was once misguidedly thought to be caused by maternal rejection. The hypothesis of a specific theory of mind deficit was a crucial step in this process. It explains the puzzle of the characteristic social and communication impairments of autism and allows for the fact that they can coexist with good general abilities. This hypothesis has been widely accepted and a start has been made at pinpointing the brain basis of theory of mind. The non-social impairments of autism have now become a major focus for cognitive research. One theory proposes dysfunction in executive processes, in an attempt to explain repetitive behaviour and inflexibility. Another theory proposes weak information integration, in an attempt to explain narrow interests and special talents. Autism research has thus stimulated ideas on important mind-brain systems that may be dedicated to the development of social awareness, executive functions and integrative processing.

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.

Fractionation of visual memory: evidence from a case with multiple neurodevelopmental impairments.

It is known that the adult visual memory system is fractionable into functionally independent cognitive subsystems, selectively susceptible to brain damage. However, it is unclear whether these cognitive subsystems can fractionate developmentally. The present study describes an investigation of visual memory of a patient (PE) with multiple developmental disorders. PE was congenitally deaf, had Gilles de la Tourette syndrome and autism, with non-verbal ability in the normal range. The patient presented with a recognition memory impairment for unknown human faces. This contrasted with his superior recognition memory for unknown buildings, landscapes and outdoor scenes. PE's memory impairment for faces could not be explained by a general deficit in face processing. Interestingly, PE also showed a recognition memory impairment for animals. These findings indicate that different domains of the visual memory system can be fractionated developmentally. In particular, it demonstrates that topographical memory can develop independently from other aspects of visual memory.

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.

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'.

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.

Prospects for a cognitive neuropsychology of autism: Hobson's choice.

Leslie (1987b) proposed a new, metarepresentational model for the cognition of pretense. This model identified a cognitive component necessary for the normal development of a "theory of mind." In this article, the relation of the child's early affective sensitivities to this component is considered. Early affective sensitivities seem to be cognitively distinct from the metarepresentational component. Childhood autism provides an interesting opportunity to study this problem. Three theoretical possibilities for the pathogenesis of this condition are presented: (a) a basic affective disorder as proposed by Hobson (this issue, p. 114), (b) a basic affective disorder and a basic cognitive disorder jointly, and (c) a basic cognitive disorder. There is little evidence for Option a, and a growing body of evidence supports Option c. Option b is sidelined for the time being on grounds of parsimony. Leslie's original theoretical proposals are revised, and some resulting implications are presented for the future investigation of the cognitive neuropsychology of autism.

Autism: beyond "theory of mind".

The theory of mind account of autism has been remarkably successful in making specific predictions about the impairments in socialization, imagination and communication shown by people with autism. It cannot, however, explain either the non-triad features of autism, or earlier experimental findings of abnormal assets and deficits on non-social tasks. These unexplained aspects of autism, and the existence of autistic individuals who consistently pass false belief tasks, suggest that it may be necessary to postulate an additional cognitive abnormality. One possible abnormality-weak central coherence--is discussed, and preliminary evidence for this theory is presented.

The impact of orthographic consistency on dyslexia: a German-English comparison.

We examined reading and phonological processing abilities in English and German dyslexic children, each compared with two control groups matched for reading level (8 years) and age (10-12 years). We hypothesised that the same underlying phonological processing deficit would exist in both language groups, but that there would be differences in the severity of written language impairments, due to differences in orthographic consistency. We also hypothesized that systematic differences due to orthographic consistency should be found equally for normal and dyslexic readers. All cross-language comparisons were based on a set of stimuli matched for meaning, pronunciation and spelling. The results supported both hypotheses: On a task challenging phonological processing skills (spoonerisms) both English and German dyslexics were significantly impaired compared to their age and reading age controls. However, there were extremely large differences in reading performance when English and German dyslexic children were compared. The evidence for systematic differences in reading performance due to differences in orthographic consistency was similar for normal and for dyslexic children, with English showing marked adverse effect on acquisition of reading skills.

Other minds in the brain: a functional imaging study of "theory of mind" in story comprehension.

The ability of normal children and adults to attribute independent mental states to self and others in order to explain and predict behaviour ("theory of mind") has been a focus of much recent research. Autism is a biologically based disorder which appears to be characterised by a specific impairment in this "mentalising" process. The present paper reports a functional neuroimaging study with positron emission tomography in which we studied brain activity in normal volunteers while they performed story comprehension tasks necessitating the attribution of mental states. The resultant brain activity was compared with that measured in two control tasks: "physical" stories which did not require this mental attribution, and passages of unlinked sentences. Both story conditions, when compared to the unlinked sentences, showed significantly increased regional cerebral blood flow in the following regions: the temporal poles bilaterally, the left superior temporal gyrus and the posterior cingulate cortex. Comparison of the "theory of mind" stories with "physical" stores revealed a specific pattern of activation associated with mental state attribution: it was only this task which produced activation in the medial frontal gyrus on the left (Brodmann's area 8). This comparison also showed significant activation in the posterior cingulate cortex. These surprisingly clear-cut findings are discussed in relation to previous studies of brain activation during story comprehension. The localisation of brain regions involved in normal attribution of mental states and contextual problem solving is feasible and may have implication for the neural basis of autism.

The neuroanatomy of autism: a voxel-based whole brain analysis of structural scans.

Autism is a biological disorder which affects social cognition, and understanding brain abnormalities of the former will elucidate the brain basis of the latter. We report structural MRI data on 15 high-functioning individuals with autistic disorder. A voxel-based whole brain analysis identified grey matter differences in an amygdala centered system relative to 15 age- and IQ-matched controls. Decreases of grey matter were found in anterior parts of this system (right paracingulate sulcus, left inferior frontal gyrus). Increases were found in posterior parts (amygdala/peri-amygdaloid cortex, middle temporal gyrus, inferior temporal gyrus), and in regions of the cerebellum. These structures are implicated in social cognition by animal, imaging and histopathological studies. This study therefore provides converging evidence of the physiological basis of social cognition.

'Theory of mind' in the brain. Evidence from a PET scan study of Asperger syndrome.

The ability to attribute mental states to others ('theory of mind') pervades normal social interaction and is impaired in autistic individuals. In a previous positron emission tomography scan study of normal volunteers, performing a 'theory of mind' task was associated with activity in left medial prefrontal cortex. We used the same paradigm in five patients with Asperger syndrome, a mild variant of autism with normal intellectual functioning. No task-related activity was found in this region, but normal activity was observed in immediately adjacent areas. This result suggests that a highly circumscribed region of left medial prefrontal cortex is a crucial component of the brain system that underlies the normal understanding of other minds.

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.

The understanding and use of interpersonal gestures by autistic and Down's syndrome children.

Autistic adolescents with mild, moderate, and severe degrees of mental retardation, Down's syndrome adolescents, and clinically normal 4-, 5-, and 6-year-old children were compared in their ability to understand a set of simple instrumental gestures. Almost all gestures were perfectly understood, that is, correctly responded to, by normal children from age 5 onwards, and by all the handicapped groups, regardless of diagnosis or degree of retardation. However, the ability to initiate such gestures on verbal request was generally less good, especially in the less able autistic groups. The same subjects were unobtrusively observed in the playground and during mealtime at their schools. Peer interactions were least frequent in the autistic subjects, regardless of degree of mental retardation. However, relative to interaction frequency, the autistic group used nonverbal instrumental gestures as a means of communication to the same extent as the other groups. Unlike Down's syndrome adolescents, or normal preschool children, no autistic adolescent ever used expressive gestures.