γ-band abnormalities as markers of autism spectrum disorders.

Autism is a behaviorally diagnosed neurodevelopmental disorder with no current biomarkers with high specificity and sensitivity. γ-band abnormalities have been reported in many studies of autism spectrum disorders. γ-band activity is associated with perceptual and cognitive functions that are compromised in autism. Some γ-band deficits have also been seen in unaffected first-degree relatives, suggesting heritability of these findings. This review covers the published literature on γ abnormalities in autism, the proposed mechanisms underlying the deficits and the potential for translation into new treatments. Although the utility of γ-band metrics as diagnostic biomarkers is currently limited, such changes in autism are also useful as endophenotypes, for evaluating potential neural mechanisms, and for use as surrogate markers of treatment response to interventions.

Greater neuronal responses during automatic semantic processing in schizophrenia.

A core feature of schizophrenia is a disturbance of associative processes. To date, no functional MRI studies have investigated semantic priming in schizophrenia under experimental conditions that measure automatic, as opposed to strategic, processing. The present study's focus was to investigate hemodynamic responses during indirect semantic priming at a short stimulus onset asynchrony (i.e., 350 ms), conditions which are considered to be a particularly sensitive measure of automatic spreading activation during semantic processing and of the associative disturbances in schizophrenia. Seventeen individuals with DSM-IV, schizophrenia and 15 comparison participants underwent functional scanning while performing a lexical decision task on directly related, indirectly related, unrelated, and word/nonword pairs. A random-effects region of interest analysis within a priori temporal and frontal regions was performed. Whereas comparison individuals exhibited hemodynamic suppression in response to priming, individuals with schizophrenia exhibited hemodynamic enhancement. Relative to the comparison group, these enhancements were observed in the left fusiform and superior temporal gyri for indirectly related word pairs relative to unrelated pairs. Greater priming-related responses within temporal regions may reflect increased and prolonged automatic spreading activation during semantic processing in schizophrenia.

Phonological processing in first-degree relatives of individuals with autism: an fMRI study.

Autism spectrum disorders (ASD) are complex neurodevelopmental disorders. Twin studies have provided heritability estimates as high as 90% for idiopathic ASD. Further evidence for the spectrum's heritability is provided by the presence of the broad autism phenotype (BAP) in unaffected first-degree relatives. Language ability, specifically phonological processing, is proposed to be a core BAP trait. To date, however, no functional neuroimaging investigations of phonological processing in relatives of individuals with ASD have been undertaken. We conducted a functional magnetic resonance imaging (fMRI) study in parents of children with ASD utilizing a priming task probing implicit phonological processing. In our condition that placed heavier demands on phonological recoding, parents exhibited greater hemodynamic responses than controls in a network of cortical regions involved in phonological processing. Across conditions, parents exhibited enhanced priming-induced response suppression suggesting compensatory neural processing. A nonword repetition test used in previous studies of relatives was also administered. Correlations between this measure and our functional measures also suggested compensatory processing in parents. Regions exhibiting atypical responses in parents included regions previously implicated in the spectrum's language impairments and found to exhibit structural abnormalities in a parent study. These results suggest a possible neurobiological substrate of the phonological deficits proposed to be a core BAP trait. However, these results should be considered preliminary. No previous fMRI study has investigated phonological processing in ASD, so replication is required. Furthermore, interpretation of our fMRI results is limited by the fact that the parent group failed to exhibit behavioral evidence of phonological impairments.

Transient and steady-state auditory gamma-band responses in first-degree relatives of people with autism spectrum disorder.

BACKGROUND: Stimulus-related γ-band oscillations, which may be related to perceptual binding, are reduced in people with autism spectrum disorders (ASD). The purpose of this study was to examine auditory transient and steady-state γ-band findings in first-degree relatives of people with ASD to assess the potential familiality of these findings in ASD. METHODS: Magnetoencephalography (MEG) recordings in 21 parents who had a child with an autism spectrum disorder (pASD) and 20 healthy adult control subjects (HC) were obtained. Gamma-band phase locking factor (PLF), and evoked and induced power to 32, 40 and 48 Hz amplitude-modulated sounds were measured for transient and steady-state responses. Participants were also tested on a number of behavioral and cognitive assessments related to the broad autism phenotype (BAP). RESULTS: Reliable group differences were seen primarily for steady-state responses. In the left hemisphere, pASD subjects exhibited lower phase-locked steady-state power in all three conditions. Total γ-band power, including the non-phase-locked component, was also reduced in the pASD group. In addition, pASD subjects had significantly lower PLF than the HC group. Correlations were seen between MEG measures and BAP measures. CONCLUSIONS: The reduction in steady-state γ-band responses in the pASD group is consistent with previous results for children with ASD. Steady-state responses may be more sensitive than transient responses to phase-locking errors in ASD. Together with the lower PLF and phase-locked power in first-degree relatives, correlations between γ-band measures and behavioral measures relevant to the BAP highlight the potential of γ-band deficits as a potential new autism endophenotype.

Implicit phonological priming during visual word recognition.

Phonology is a lower-level structural aspect of language involving the sounds of a language and their organization in that language. Numerous behavioral studies utilizing priming, which refers to an increased sensitivity to a stimulus following prior experience with that or a related stimulus, have provided evidence for the role of phonology in visual word recognition. However, most language studies utilizing priming in conjunction with functional magnetic resonance imaging (fMRI) have focused on lexical-semantic aspects of language processing. The aim of the present study was to investigate the neurobiological substrates of the automatic, implicit stages of phonological processing. While undergoing fMRI, eighteen individuals performed a lexical decision task (LDT) on prime-target pairs including word-word homophone and pseudoword-word pseudohomophone pairs with a prime presentation below perceptual threshold. Whole-brain analyses revealed several cortical regions exhibiting hemodynamic response suppression due to phonological priming including bilateral superior temporal gyri (STG), middle temporal gyri (MTG), and angular gyri (AG) with additional region of interest (ROI) analyses revealing response suppression in the left lateralized supramarginal gyrus (SMG). Homophone and pseudohomophone priming also resulted in different patterns of hemodynamic responses relative to one another. These results suggest that phonological processing plays a key role in visual word recognition. Furthermore, enhanced hemodynamic responses for unrelated stimuli relative to primed stimuli were observed in midline cortical regions corresponding to the default-mode network (DMN) suggesting that DMN activity can be modulated by task requirements within the context of an implicit task.

A voxel-based morphometry comparison of regional gray matter between fragile X syndrome and autism.

The phenotypic association between fragile X syndrome (FXS) and autism is well established, but no studies have directly compared whole-brain anatomy between the two disorders. We performed voxel-based morphometry analyses of magnetic resonance imaging (MRI) scans on 10 individuals with FXS, 10 individuals with autism, and 10 healthy comparison subjects to identify volumetric changes in each disorder. Regional gray matter volumes within frontal, parietal, temporal, and cingulate gyri, as well as in the caudate nuclei and cerebellum, were larger in the FXS group relative to the autism group. In addition, volume increases in FXS were observed in frontal gyri and caudate nuclei compared to controls. The autism group exhibited volume increases in frontal and temporal gyri relative to the FXS group, and no volume increases relative to controls. Volumetric deficits relative to controls were observed in regions of the cerebellum for both groups, with additional deficits in parietal and temporal gyri for the FXS group. Our caudate nuclei and frontal gyri results may implicate dysfunction of frontostriatal circuitry in FXS. Cerebellar deficits suggest atypical development of the cerebellum contributing to the phenotype of both disorders, but further imply that unique cerebellar regions contribute to the phenotype of each disorder.