Biomedical subjects

Mirella Dapretto

Publications and source records attributed to Mirella Dapretto.

9 recordsLinked to original sources

PubMed2026

Excitation/inhibition balance subtypes in autism and their genetic, neural, and clinical profiles.

Excitation (E)/inhibition (I) imbalance is considered a key mechanism in Autism Spectrum Disorder (ASD). However, E/I imbalance can have different etiologies with increased E relative to I (E > I) and increased I relative to E (E < I). Both neural profiles can be associated with altered clinical phenotype, suggesting "bell"-shape brain-behavior relationships. We derived E/I balance measures from resting-state EEG in a large sex-balanced sample of youths with and without autism (N = 310; 164 youths with ASD and 146 typically developing (TD) youths) to address group discriminative power of neural markers, their relation to social skills, and the potential to define different neural subtypes within the autistic group. We also conducted genome-wide copy number variant (CNV) and gene expression analyses to provide additional insight into distinct neural subtypes in autism. A high-density 128-channel electroencephalography (EEG) was used to register neural activity of participants, blood samples were collected from the ASD youths to obtain genomic DNA, and rich behavioral phenotyping was provided for each participant. The results revealed three subgroups within the autistic cohort with the presence of "typical" E/I, E > I, and E < I neural profiles. The two subgroups with E/I imbalance had altered clinical phenotypes. In addition, these subgroups had different genetic profiles, showing that genes within identified CNVs had distinct expression patterns with the evidence of more prenatal (E < I) vs. postnatal (E > I) gene expression. The study suggests that the proposed clustering approach has relevance for the identification of clinically meaningful neural and genetic subtypes within a heterogeneous autistic cohort.

Autism spectrum disorder↗

PubMed2006

The mirror neuron system and the consequences of its dysfunction.

The discovery of premotor and parietal cells known as mirror neurons in the macaque brain that fire not only when the animal is in action, but also when it observes others carrying out the same actions provides a plausible neurophysiological mechanism for a variety of important social behaviours, from imitation to empathy. Recent data also show that dysfunction of the mirror neuron system in humans might be a core deficit in autism, a socially isolating condition. Here, we review the neurophysiology of the mirror neuron system and its role in social cognition and discuss the clinical implications of mirror neuron dysfunction.

Animals↗

PubMed2006

Cracking the language code: neural mechanisms underlying speech parsing.

Word segmentation, detecting word boundaries in continuous speech, is a critical aspect of language learning. Previous research in infants and adults demonstrated that a stream of speech can be readily segmented based solely on the statistical and speech cues afforded by the input. Using functional magnetic resonance imaging (fMRI), the neural substrate of word segmentation was examined on-line as participants listened to three streams of concatenated syllables, containing either statistical regularities alone, statistical regularities and speech cues, or no cues. Despite the participants' inability to explicitly detect differences between the speech streams, neural activity differed significantly across conditions, with left-lateralized signal increases in temporal cortices observed only when participants listened to streams containing statistical regularities, particularly the stream containing speech cues. In a second fMRI study, designed to verify that word segmentation had implicitly taken place, participants listened to trisyllabic combinations that occurred with different frequencies in the streams of speech they just heard ("words," 45 times; "partwords," 15 times; "nonwords," once). Reliably greater activity in left inferior and middle frontal gyri was observed when comparing words with partwords and, to a lesser extent, when comparing partwords with nonwords. Activity in these regions, taken to index the implicit detection of word boundaries, was positively correlated with participants' rapid auditory processing skills. These findings provide a neural signature of on-line word segmentation in the mature brain and an initial model with which to study developmental changes in the neural architecture involved in processing speech cues during language learning.

Adult↗

PubMed2006

Neural basis of irony comprehension in children with autism: the role of prosody and context.

While individuals with autism spectrum disorders (ASD) are typically impaired in interpreting the communicative intent of others, little is known about the neural bases of higher-level pragmatic impairments. Here, we used functional MRI (fMRI) to examine the neural circuitry underlying deficits in understanding irony in high-functioning children with ASD. Participants listened to short scenarios and decided whether the speaker was sincere or ironic. Three types of scenarios were used in which we varied the information available to guide this decision. Scenarios included (i) both knowledge of the event outcome and strong prosodic cues (sincere or sarcastic intonation), (ii) prosodic cues only or (iii) knowledge of the event outcome only. Although children with ASD performed well above chance, they were less accurate than typically developing (TD) children at interpreting the communicative intent behind a potentially ironic remark, particularly with regard to taking advantage of available contextual information. In contrast to prior research showing hypoactivation of regions involved in understanding the mental states of others, children with ASD showed significantly greater activity than TD children in the right inferior frontal gyrus (IFG) as well as in bilateral temporal regions. Increased activity in the ASD group fell within the network recruited in the TD group and may reflect more effortful processing needed to interpret the intended meaning of an utterance. These results confirm that children with ASD have difficulty interpreting the communicative intent of others and suggest that these individuals can recruit regions activated as part of the normative neural circuitry when task demands require explicit attention to socially relevant cues.

Adolescent↗

PubMed2005

Understanding emotions in others: mirror neuron dysfunction in children with autism spectrum disorders.

To examine mirror neuron abnormalities in autism, high-functioning children with autism and matched controls underwent fMRI while imitating and observing emotional expressions. Although both groups performed the tasks equally well, children with autism showed no mirror neuron activity in the inferior frontal gyrus (pars opercularis). Notably, activity in this area was inversely related to symptom severity in the social domain, suggesting that a dysfunctional 'mirror neuron system' may underlie the social deficits observed in autism.

Autistic Disorder↗

PubMed2005

A functional magnetic resonance imaging study of discourse coherence in typically developing children.

Using functional magnetic resonance imaging and a previously validated activation paradigm, we investigated the neural networks involved in detecting discourse coherence in a sample of typically developing children. Study participants listened to short question-answer dialogues and determined whether the answers made sense. Consistent with prior adult findings, when this decision involved an implicit appraisal of the conversation logic, frontotemporal activity was strongly left lateralized. In contrast, when this determination involved detecting a change in the conversation topic, activity in frontotemporal regions was bilateral, with a right hemisphere bias. Despite behavioral performance differences, children and adults showed remarkably similar activation profiles when making sense of conversation, indicating that the neural architecture subserving this fundamental communicative function is established relatively early during normal development.

Cerebral Cortex↗

PubMed2005

Metaphorical vs. literal word meanings: fMRI evidence against a selective role of the right hemisphere.

The neural networks associated with processing metaphorical word meanings were investigated in normal adults using fMRI. Subjects listened to sets of three adjectives and decided whether the last two had a similar meaning. One condition required accessing the literal meaning of the middle word (e.g., hot-cold-chilly), whereas the other condition required accessing its nonliteral, or metaphorical, meaning (e.g., hot-cold-unfriendly). Direct comparison of the nonliteral vs. literal condition showed reliable activity only in left prefrontal and temporo-parietal regions. These results argue against a selective role of the right hemisphere (RH) in accessing metaphorical word meanings. In line with a growing literature, these findings suggest that prior reports of greater RH involvement for metaphorical language might reflect the increased complexity of figurative language rather than an RH specialization for understanding metaphors.

Adult↗

PubMed2004

The neural correlates of grammatical gender decisions in Spanish.

In the current study, nine participants were asked to make gender decisions for a set of Spanish nouns while being scanned with functional MRI (fMRI). Words were chosen in which a direct mapping between ending and gender ("transparent" items such as carro(fem) or casa(masc)) is present and those in which there is not a direct relationship ("opaque" items such as fuente(fem) or arroz(masc)). Direct comparisons between opaque and transparent words revealed increased activity in left BA44/45, and BA44/6 as well as bilateral activation near BA 47/insula and the anterior cingulate gyrus. These results reveal activity in areas previously found to be devoted to articulation of the determiner and to morphological processing. Taken together they support the notion that gender decisions for opaque items requires deeper and more effortful processing during the retrieval of lexical and syntactic information.

Adult↗

PubMed2004

Neural correlates of facial affect processing in children and adolescents with autism spectrum disorder.

OBJECTIVE: To examine the neural basis of impairments in interpreting facial emotions in children and adolescents with autism spectrum disorders (ASD). METHOD: Twelve children and adolescents with ASD and 12 typically developing (TD) controls matched faces by emotion and assigned a label to facial expressions while undergoing functional magnetic resonance imaging. RESULTS: Both groups engaged similar neural networks during facial emotion processing, including activity in the fusiform gyrus (FG) and prefrontal cortex. However, between-group analyses in regions of interest revealed that when matching facial expressions, the ASD group showed significantly less activity than the TD group in the FG, but reliably greater activity in the precuneus. During the labeling of facial emotions, no between-group differences were observed at the behavioral or neural level. Furthermore, activity in the amygdala was moderated by task demands in the TD group but not in the ASD group. CONCLUSIONS: These findings suggest that children and adolescents with ASD in part recruit different neural networks and rely on different strategies when processing facial emotions. High-functioning individuals with ASD may be relatively unimpaired in the cognitive assessment of basic emotions, yet still show differences in the automatic processing of facial expressions.

Adolescent↗