Executive Function Brain Network Activation Predicts Driving Hazard Detection in ADHD.

Drivers with neurodevelopmental disorders (NDDs), such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are at increased risk of experiencing driving difficulties. An important aspect of driving safety and skill involves hazard detection. This functional magnetic resonance imaging study examined the neural responses associated with driving hazard detection in drivers with ASD, ADHD, and typically developing (TD) drivers. Forty participants (12 ASD, 15 ADHD, 13 TD) ages 16-30 years completed a driving simulator task in which they encountered social and nonsocial hazards; reaction time (RT) for responding to hazards was measured. Participants then completed a similar hazard detection task in the MRI scanner so that neural response to hazards could be measured. Activation of regions of interest considered part of the executive function (EF) and theory of mind (ToM) networks were examined and related to driving simulator behavior. Results showed that stronger activation of the EF network during social hazard processing, including the bilateral dorsolateral prefrontal cortex and posterior parietal cortex, was associated with faster RT to social hazards among drivers with ADHD, but not among drivers with ASD. This provides the first evidence of a relationship between EF network brain activation and driving skills in ADHD and suggests that alterations in this network may underlie driving behavior. In comparison, the current study did not observe a relationship between ToM network activation and RT to social hazards in any group. This study lays the groundwork for relating neural activation to driving behavior among individuals with NDDs.

A method for pre-operative single-subject thalamic segmentation based on probabilistic tractography for essential tremor deep brain stimulation.

PURPOSE: Deep brain stimulation is a common treatment for medication-refractory essential tremor. Current coordinate-based targeting methods result in variable outcomes due to variation in thalamic structure and the optimal patient-specific functional location. The purpose of this study was to compare the coordinate-based pre-operative targets to patient-specific thalamic segmentation utilizing a probabilistic tractography methodology. METHODS: Using available diffusion MRI of 32 subjects from the Human Connectome Project database, probabilistic tractography was performed. Each thalamic voxel was coded based on one of six predefined cortical targets. The segmentation results were analyzed and compared to a 2-mm spherical target centered at the coordinate-based location of the ventral intermediate thalamic nucleus. RESULTS: The traditional coordinate-based target had maximal overlap with the junction of the region most connected to primary motor cortex (M1) (36.6 ± 25.7% of voxels on left; 58.1 ± 28.5% on right) and the area connected to the supplementary motor area/premotor cortex (SMA/PMC) (44.9 ± 21.7% of voxels on left; 28.9 ± 22.2% on right). There was a within-subject coefficient of variation from right-to-left of 69.4 and 63.1% in the volume of overlap with the SMA/PMC and M1 regions, respectively. CONCLUSION: Thalamic segmentation based on structural connectivity measures is a promising technique that may enhance traditional targeting methods by generating reproducible, patient-specific pre-operative functional targets. Our results highlight the problematic intra- and inter-subject variability of indirect, coordinate-based targets. Future prospective clinical studies will be needed to validate this targeting methodology in essential tremor patients.

Differences in resting cerebellar and prefrontal cortical blood flow in spinal cord injury-related neuropathic pain: A brief report.

Context: Little is understood about differences in resting neural activity among those with spinal cord injury (SCI)-related neuropathic pain. The purpose of this pilot study was to determine resting cerebral blood flow differences in persons with SCI-related neuropathic pain compared to healthy, pain-free able-bodied controls.Methods: Five persons with paraplegia and ten able-bodied participants were included in this study. Resting blood flow, as measured by a continuous arterial spin labeling (ASL) method of fMRI, was analyzed via statistical parametric mapping.Results: Persons with SCI-related neuropathic pain had significantly lower resting blood flow in the cerebellum (Crus I/II), rostral ventromedial medulla and left insular cortex. In contrast, greater resting blood flow occurred in the medial orbitofrontal cortex among those with SCI-related neuropathic pain compared to controls.Conclusion: Differences in resting blood flow were observed among those with SCI-related pain, particularly in regions that may be involved in affective-motivational and cognitive-evaluative aspects of pain. Larger ASL studies in addition to functional connectivity studies using fMRI are needed to clarify unique neural patterns in this complex and often intractable form of pain.

Ictogenesis during sEEG evaluation after acute intracranial hemorrhage.

We present a unique case of a patient with drug-resistant focal epilepsy undergoing stereoelectroencephalography (sEEG) who developed an acute posttraumatic intracranial hemorrhage during monitoring, first detected by changes on sEEG. Our case demonstrates the evolution of electrographic changes at the time of initial hemorrhage to the development of ictal activity. We conducted spectral analysis of the sEEG data to illustrate the transition from an interictal to ictal state. Initially, delta power increased in the region of acute hemorrhage, followed by sustained regional reduction in frequency variability. Our findings provide further information on the development of epileptiform activity in acute hemorrhage.

The Action Imitation network and motor imitation in children and adolescents with autism.

While deficits in imitation had been reported in children with autism spectrum disorder (ASD), its exact nature remains unclear. A dysfunction in mirroring mechanisms (through action imitation) has been proposed by some studies to explain this, although some recent evidence points against this hypothesis. The current study used behavior and functional MRI to examine the integrated functioning of the regions that are considered part of the Action Imitation network (AIN) in children and adolescents with ASD during a motor imitation task. Fourteen ASD and 15 age-and-IQ-matched typically developing (TD) children were asked to imitate a series of hand gestures in the MRI scanner. Intact performance on imitation (accurate imitation of hand gestures outside the scanner) in both ASD and TD groups was accompanied by significantly lower activity in ASD participants, relative to TD, in right angular gyrus, precentral gyrus, and left middle cingulate. In addition, autism traits were found to be significantly correlated with activation in the right angular gyrus. Overall, the findings of this study support the role of AIN in imitation and a potential difference in the recruitment of this network in ASD children.

Neural networks underlying language and social cognition during self-other processing in Autism spectrum disorders.

The social communication impairments defining autism spectrum disorders (ASD) may be built upon core deficits in perspective-taking, language processing, and self-other representation. Self-referential processing entails the ability to incorporate self-awareness, self-judgment, and self-memory in information processing. Very few studies have examined the neural bases of integrating self-other representation and semantic processing in individuals with ASD. The main objective of this functional MRI study is to examine the role of language and social brain networks in self-other processing in young adults with ASD. Nineteen high-functioning male adults with ASD and 19 age-sex-and-IQ-matched typically developing (TD) control participants made "yes" or "no" judgments of whether an adjective, presented visually, described them (self) or their favorite teacher (other). Both ASD and TD participants showed significantly increased activity in the medial prefrontal cortex (MPFC) during self and other processing relative to letter search. Analyses of group differences revealed significantly reduced activity in left inferior frontal gyrus (LIFG), and left inferior parietal lobule (LIPL) in ASD participants, relative to TD controls. ASD participants also showed significantly weaker functional connectivity of the anterior cingulate cortex (ACC) with several brain areas while processing self-related words. The LIFG and IPL are important regions functionally at the intersection of language and social roles; reduced recruitment of these regions in ASD participants may suggest poor level of semantic and social processing. In addition, poor connectivity of the ACC may suggest the difficulty in meeting the linguistic and social demands of this task in ASD. Overall, this study provides new evidence of the altered recruitment of the neural networks underlying language and social cognition in ASD.

The Impact of Reading Intervention on Brain Responses Underlying Language in Children With Autism.

Deficits in language comprehension have been widely reported in children with autism spectrum disorders (ASD), with behavioral and neuroimaging studies finding increased reliance on visuospatial processing to aid in language comprehension. However, no study to date, has taken advantage of this strength in visuospatial processing to improve language comprehension difficulties in ASD. This study used a translational neuroimaging approach to test the role of a visual imagery-based reading intervention in improving the brain circuitry underlying language processing in children with ASD. Functional magnetic resonance imaging (MRI), in a longitudinal study design, was used to investigate intervention-related change in sentence comprehension, brain activation, and functional connectivity in three groups of participants (age 8-13 years): an experimental group of ASD children (ASD-EXP), a wait-list control group of ASD children (ASD-WLC), and a group of typically developing control children. After intervention, the ASD-EXP group showed significant increase in activity in visual and language areas and right-hemisphere language area homologues, putamen, and thalamus, suggestive of compensatory routes to increase proficiency in reading comprehension. Additionally, ASD children who had the most improvement in reading comprehension after intervention showed greater functional connectivity between left-hemisphere language areas, the middle temporal gyrus and inferior frontal gyrus while reading high imagery sentences. Thus, the findings of this study, which support the principles of dual coding theory [Paivio 2007], suggest the potential of a strength-based reading intervention in changing brain responses and facilitating better reading comprehension in ASD children.

White Matter Diffusion of Major Fiber Tracts Implicated in Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder found to have widespread alterations in the function and synchrony of brain regions. These differences may underlie alterations in microstructural organization, such as in white matter pathways. To investigate the diffusion of major white matter tracts, the current study examined multiple indices of white matter diffusion in 42 children and adults with ASD and 44 typically developing (TD) age- and IQ-matched peers using diffusion tensor imaging. Diffusivity measures were compared between groups for the following tracts: bilateral cingulum bundle, corpus callosum, inferior longitudinal fasciculus, superior longitudinal fasciculus, and uncinate fasciculus. Results indicate a significant reduction in fractional anisotropy (FA) for the left superior longitudinal fasciculus (LSLF) in ASD children and adults compared with TD peers. A significant increase in radial diffusivity for ASD participants was also found in the same cluster along the LSLF. In addition, a significant positive correlation emerged for all subjects between FA for the LSLF and age, with FA increasing with age. These findings point to a significant alteration in long-distance white matter connectivity in children and adults with ASD, potentially underscoring the relationship between alterations in white matter diffusion and the ASD phenotype. These results also suggest that the white matter alterations in autism may be subtle and related to the developmental trajectory.

Functional brain networks and white matter underlying theory-of-mind in autism.

Human beings constantly engage in attributing causal explanations to one's own and to others' actions, and theory-of-mind (ToM) is critical in making such inferences. Although children learn causal attribution early in development, children with autism spectrum disorders (ASDs) are known to have impairments in the development of intentional causality. This functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) study investigated the neural correlates of physical and intentional causal attribution in people with ASDs. In the fMRI scanner, 15 adolescents and adults with ASDs and 15 age- and IQ-matched typically developing peers made causal judgments about comic strips presented randomly in an event-related design. All participants showed robust activation in bilateral posterior superior temporal sulcus at the temporo-parietal junction (TPJ) in response to intentional causality. Participants with ASDs showed lower activation in TPJ, right inferior frontal gyrus and left premotor cortex. Significantly weaker functional connectivity was also found in the ASD group between TPJ and motor areas during intentional causality. DTI data revealed significantly reduced fractional anisotropy in ASD participants in white matter underlying the temporal lobe. In addition to underscoring the role of TPJ in ToM, this study found an interaction between motor simulation and mentalizing systems in intentional causal attribution and its possible discord in autism.

Surface-based morphometry of the cortical architecture of autism spectrum disorders: volume, thickness, area, and gyrification.

Structural neuroimaging studies of autism spectrum disorder (ASD) have uncovered widespread neuroanatomical abnormalities, which may have a significant impact on brain function, connectivity, and on behavioral symptoms of autism. The findings of previous structural MRI studies have largely been distributed across several brain areas, with limited consistency. The current study examined neuroanatomical abnormalities by comparing surface-based measures of cortical morphology (CT: cortical thickness, CSA: cortical surface area, CV: cortical volume, and GI: gyrification index) in 55 high-functioning children and adults with ASD to 60 age-and-IQ-matched typically developing (TD) peers. A few brain areas, the fusiform gyrus (FG), middle temporal gyrus (MTG), and inferior frontal gyrus (IFG), emerged to be primarily different in their morphology between the two groups. Compared to TD participants, ASD participants had significantly smaller CV in left MTG, reduced CSA in bilateral MTG and FG, reduced GI in left supramarginal gyrus, and significantly increased CT in the pars opercularis of the IFG. As a function of age, ASD participants had significant reductions in: CT in the pars opercularis, CSA of the left rostral middle frontal gyrus, and GI for left supramarginal gyrus. Thus, alterations in cortical morphology in ASD were seen primarily in regions that are considered part of the social brain. Overall, these findings point to: neuroanatomical alterations in social brain areas, developmental differences in neuroanatomy, and the need to study neuroanatomy at multiple levels in order to better characterize the cortical architecture of ASD.

The role of mirroring and mentalizing networks in mediating action intentions in autism.

BACKGROUND: The ability to interpret agents' intent from their actions is a vital skill in successful social interaction. However, individuals with autism spectrum disorders (ASD) have been found to have difficulty in attributing intentions to others. The present study investigated the neural mechanisms of inferring intentions from actions in individuals with ASD. METHODS: Functional magnetic resonance imaging (fMRI) data were acquired from 21 high-functioning young adults with ASD and 22 typically developing (TD) control participants, while making judgments about the means (how an action is performed) and intention (why an action is performed) of a model's actions. RESULTS: Across both groups of participants, the middle and superior temporal cortex, extending to temporoparietal junction, and posterior cingulate cortex, responded significantly to inferring the intent of an action, while inferior parietal lobule and occipital cortices were active for judgments about the means of an action. Participants with ASD had significantly reduced activation in calcarine sulcus and significantly increased activation in left inferior frontal gyrus, compared to TD peers, while attending to the intentions of actions. Also, ASD participants had weaker functional connectivity between frontal and posterior temporal regions while processing intentions. CONCLUSIONS: These results suggest that processing actions and intentions may not be mutually exclusive, with reliance on mirroring and mentalizing mechanisms mediating action understanding. Overall, inferring information about others' actions involves activation of the mirror neuron system and theory-of-mind regions, and this activation (and the synchrony between activated brain regions) appears altered in young adults with ASD.

Identification of neural connectivity signatures of autism using machine learning.

Alterations in interregional neural connectivity have been suggested as a signature of the pathobiology of autism. There have been many reports of functional and anatomical connectivity being altered while individuals with autism are engaged in complex cognitive and social tasks. Although disrupted instantaneous correlation between cortical regions observed from functional MRI is considered to be an explanatory model for autism, the causal influence of a brain area on another (effective connectivity) is a vital link missing in these studies. The current study focuses on addressing this in an fMRI study of Theory-of-Mind (ToM) in 15 high-functioning adolescents and adults with autism and 15 typically developing control participants. Participants viewed a series of comic strip vignettes in the MRI scanner and were asked to choose the most logical end to the story from three alternatives, separately for trials involving physical and intentional causality. The mean time series, extracted from 18 activated regions of interest, were processed using a multivariate autoregressive model (MVAR) to obtain the causality matrices for each of the 30 participants. These causal connectivity weights, along with assessment scores, functional connectivity values, and fractional anisotropy obtained from DTI data for each participant, were submitted to a recursive cluster elimination based support vector machine classifier to determine the accuracy with which the classifier can predict a novel participant's group membership (autism or control). We found a maximum classification accuracy of 95.9% with 19 features which had the highest discriminative ability between the groups. All of the 19 features were effective connectivity paths, indicating that causal information may be critical in discriminating between autism and control groups. These effective connectivity paths were also found to be significantly greater in controls as compared to ASD participants and consisted predominantly of outputs from the fusiform face area and middle temporal gyrus indicating impaired connectivity in ASD participants, particularly in the social brain areas. These findings collectively point toward the fact that alterations in causal connectivity in the brain in ASD could serve as a potential non-invasive neuroimaging signature for autism.