Glutamate levels of the right and left anterior cingulate cortex in autistics adults.

BACKGROUND: The neurobiology of Autism Spectrum Disorder (ASD) is still unknown. Alteration in glutamate metabolism might translate into an imbalance of the excitation/inhibition equilibrium of cortical networks that in turn are related to autistic symptoms, but previous studies using voxel located in bilateral anterior cingulate cortex (ACC) failed to show abnormalities in total glutamate level. Due to the functional differences in the right and left ACC, we sought to determine whether a difference between right and left ACC glutamate levels could be found when comparing ASD patients and control subjects. METHODS: Using single-voxel proton magnetic resonance spectroscopy (1H-MRS), we analyzed the glutamate + glutamine (Glx) concentrations in the left and right ACC of 19 ASD patients with normal IQs and 25 matched control subjects. RESULTS: No overall group differences in Glx were shown, in the left ACC (p = 0.24) or in the right ACC (p = 0.11). CONCLUSIONS: No significant alterations in Glx levels were detected in the left and right ACC in high-functioning autistic adults. In the excitatory/inhibitory imbalance framework, our data reinforce the critical need to analyze the GABAergic pathway, for better understanding of basic neuropathology in autism.

Inflexibility in Autism Spectrum Disorder: Need for certainty and atypical emotion processing share the blame.

Although ASD (Autism Spectrum Disorder) diagnosis requires the co-occurrence of socio-emotional deficits and inflexible behaviors, the interaction between these two domains remains unexplored. We used an emotional Wisconsin Card Sorting Test adapted to fMRI to explore this question. ASD and control participants matched a central card (a face) with one of four surrounding cards according to one of three rules: frame color, facial identity or expression. Feedback informed participants on whether to change or maintain the current sorting rule. For each rule, we modeled feedback onsets to change, switch (confirming the newly found rule) and maintenance events. "Bias error", which measures participants' willingness to switch, was larger in ASD participants for the emotional sorting rule. Brain activity to change events showed no group differences. In response to switch events significantly larger activity was observed for ASD participants in bilateral Inferior Parietal Sulci. Inflexibility in ASD appears characterized by the unwillingness to switch toward processing socio-emotional information, rather than a major disruption in cognitive flexibility. However, a larger activity to switch events in ASD highlights the need for a higher level of certainty before setting into a stable processing stage, which may be particularly detrimental in the highly changeable socio-emotional environment.

Neurocognitive, emotional and neuroendocrine correlates of exposure to sexual assault in women.

BACKGROUND: Survivors of sexual assault are vulnerable to long-term negative psychological and physical health outcomes, but few studies have investigated changes in cognition, emotional processing and brain function in the early stages after sexual assault. We used a multimodal approach to identify the cognitive and emotional correlates associated with sexual assault in women. METHODS: Twenty-seven female survivors of sexual assault were included within 4 weeks of the traumatic event, and they were compared with 20 age-matched controls. Participants underwent functional MRI while performing cognitive/emotional tasks (n-back, emotional go/no-go, mental imagery). We also measured diurnal salivary cortisol and conducted neuropsychological assessments of attention and memory abilities. RESULTS: Relative to the control group, the survivor group had lower levels of morning cortisol and showed attentional deficits. We observed no between-group differences in brain activation during the n-back or mental imagery tasks. During the emotional go/no-go task, however, the survivor group showed a lack of deactivation in the dorsal anterior cingulate cortex when processing emotional material, relative to neutral material. Exploratory analyses in the survivor group indicated that symptom severity was negatively associated with cerebellar activation when positive emotional (happy) content interfered with response inhibition, and positively associated with cerebellar activation when thinking of positive (happy) memories. LIMITATIONS: The small sample size was the main limitation of this study. CONCLUSION: Dysfunctions in the dorsal anterior cingulate cortex and the cerebellum may represent early functional brain modifications that alter higher cognitive processes when emotional material is involved.

Neurocognitive, emotional and neuroendocrine correlates of exposure to sexual assault in women.

BACKGROUND: Survivors of sexual assault are vulnerable to long-term negative psychological and physical health outcomes, but few studies have investigated changes in cognition, emotional processing and brain function in the early stages after sexual assault. We used a multimodal approach to identify the cognitive and emotional correlates associated with sexual assault in women. METHODS: Twenty-seven female survivors of sexual assault were included within 4 weeks of the traumatic event, and they were compared with 20 age-matched controls. Participants underwent functional MRI while performing cognitive/emotional tasks (n-back, emotional go/no-go, mental imagery). We also measured diurnal salivary cortisol and conducted neuropsychological assessments of attention and memory abilities. RESULTS: Relative to the control group, the survivors group had lower levels of morning cortisol and showed attentional deficits. We observed no between-group differences in brain activation during the n-back or mental imagery tasks. During the emotional go/no-go task, however, the survivors group showed a lack of deactivation in the dorsal anterior cingulate cortex when processing emotional material, relative to neutral material. Exploratory analyses in the survivors group indicated that symptom severity was negatively associated with cerebellar activation when positive emotional (happy) content interfered with response inhibition, and positively associated with cerebellar activation when thinking of positive (happy) memories. LIMITATIONS: The small sample size was the main limitation of this study. CONCLUSION: Dysfunctions in the dorsal anterior cingulate cortex and the cerebellum may represent early functional brain modifications that alter higher cognitive processes when emotional material is involved.

Sex-specific effects of COMT Val158Met polymorphism on corpus callosum structure: A whole-brain diffusion-weighted imaging study.

BACKGROUND: Genetic polymorphisms play a significant role in determining brain morphology, including white matter structure and may thus influence the development of brain functions. The main objective of this study was to examine the effect of Val158Met (rs4680) polymorphism of Catechol-O-Methyltransferase (COMT) gene on white matter connectivity in healthy adults. METHODS: We used a whole-brain diffusion-weighted imaging method with Tract-Based Spatial Statistics (TBSS) analysis to examine white matter structural integrity in intrinsic brain networks on a sample of healthy subjects (N = 82). RESULTS: Results revealed a sex-specific effect of COMT on corpus callosum (CC): in males only, Val homozygotes had significantly higher fractional anisotropy (FA) compared to Met-carriers. Volume-of-interest analysis showed a genotype by sex interaction on FA in genu and rostral midbody of CC, whereby Val males demonstrated higher FA than Met females. CONCLUSIONS: These results demonstrate the key effect of genes by sex interaction, rather than their individual contribution, on the corpus callosum anatomy.

Facial Expression Related vMMN: Disentangling Emotional from Neutral Change Detection.

Detection of changes in facial emotional expressions is crucial to communicate and to rapidly and automatically process possible threats in the environment. Recent studies suggest that expression-related visual mismatch negativity (vMMN) reflects automatic processing of emotional changes. In the present study we used a controlled paradigm to investigate the specificity of emotional change-detection. In order to disentangle specific responses to emotional deviants from that of neutral deviants, we presented neutral expression as standard stimulus (p = 0.80) and both angry and neutral expressions as deviants (p = 0.10, each). In addition to an oddball sequence, an equiprobable sequence was presented, to control for refractoriness and low-level differences. Our results showed that in an early time window (100-200 ms), the controlled vMMN was greater than the oddball vMMN only for the angry deviant, suggesting the importance of controlling for refractoriness and stimulus physical features in emotion related studies. Within the controlled vMMN, angry and neutral deviants both elicited early and late peaks occurring at 140 and 310 ms, respectively, but only the emotional vMMN presented sustained amplitude after each peak. By directly comparing responses to emotional and neutral deviants, our study provides evidence of specific activity reflecting the automatic detection of emotional change. This differs from broader "visual" change processing, and suggests the involvement of two partially-distinct pre-attentional systems in the detection of changes in facial expressions.

Early neurophysiological correlates of vocal versus non-vocal sound processing in adults.

Electrophysiological correlates of voice processing were studied in twenty adults by comparing auditory evoked potentials in response to voice and environmental sounds in passive condition. Both categories of stimuli elicited similar cortical auditory responses (i.e. N1, P2, N2 peaks); however these peaks were overlapped by two components specifically elicited by voice. The first component was evidenced as a positive deflection recorded over the fronto-temporal sites, and lateralized on the right hemiscalp. This fronto-temporal positivity to voice (FTPV) may constitute the electrophysiological counterpart of the activation of the temporal voice areas previously described in neuroimaging studies. The second component was recorded at occipito-temporo-parietal sites. This occipito-temporo-parietal negativity to voice might correspond to visual mental imagery of the vocal sounds or to some form of mental simulation of the action sounds (e.g. coughing). Both components began as early as 70 ms post-stimulus onset indicating a rapid discrimination of voice in our auditory environment, which might be the basis of communication functions in humans.

Atypical visual change processing in children with autism: an electrophysiological study.

Children with Autism Spectrum Disorder (ASD) may display atypical behaviors in reaction to unattended changes that occur in all sensory modalities. Atypical automatic auditory change processing has been highlighted in ASD via the analysis of mismatch negativity (MMN). The present study investigated visual deviancy detection in children with ASD in order to determine whether unusual reactions to change operate in other sensory modalities. Twelve children with ASD were presented with a passive visual oddball paradigm using dynamic stimuli. Compared to controls, children with ASD showed an earlier visual mismatch response, suggesting a hypersensitivity to visual deviancy. This study is thus consistent with the hypothesis of the existence of "general" atypical change detection processing in children with ASD that might contribute to their intolerance of change.

Electrophysiological correlates of automatic visual change detection in school-age children.

Automatic stimulus-change detection is usually investigated in the auditory modality by studying Mismatch Negativity (MMN). Although the change-detection process occurs in all sensory modalities, little is known about visual deviance detection, particularly regarding the development of this brain function throughout childhood. The aim of the present study was to examine the maturation of the electrophysiological response to unattended deviant visual stimuli in 11-year-old children. Twelve children and 12 adults were presented with a passive visual oddball paradigm using dynamic stimuli involving changes in form and motion. Visual Mismatch responses were identified over occipito-parietal sites in both groups but they displayed several differences. In adults the response clearly culminated at around 210 ms whereas in children three successive negative deflections were evidenced between 150 and 330 ms. Moreover, the main mismatch response in children was characterized by a positive component peaking over occipito-parieto-temporal regions around 450 ms after deviant stimulus onset. The findings showed that the organization of the vMMN response is not mature in 11-year-old children and that a longer time is still necessary to process simple visual deviancy at this late stage of child development.

Candidate electrophysiological endophenotypes of hyper-reactivity to change in autism.

Although resistance to change is a main feature of autism, the brain processes underlying this aspect of the disorder remain poorly understood. The aims of this study were to examine neural basis of auditory change-detection in children with autism spectrum disorders (ASD; N = 27) through electrophysiological patterns (MMN, P3a) and to test whether these are quantitatively related to intolerance of change (using the BSE-R scale). ASD displayed significantly shorter MMN latency and larger P3a than controls, indicating a greater tendency to switch attention to deviant events. These electrophysiological abnormalities were significantly more marked in children who displayed greater difficulties in tolerating change. The atypical neurophysiological mechanism of change perception identified might thus be associated with one of the hallmark behavioural manifestations of autism.