Reduced White Matter Fiber Density in Autism Spectrum Disorder.

Differences in brain networks and underlying white matter abnormalities have been suggested to underlie symptoms of autism spectrum disorder (ASD). However, robustly characterizing microstructural white matter differences has been challenging. In the present study, we applied an analytic technique that calculates structural metrics specific to differently-oriented fiber bundles within a voxel, termed "fixels". Fixel-based analyses were used to compare diffusion-weighted magnetic resonance imaging data from 25 individuals with ASD (mean age = 16.8 years) and 27 typically developing age-matched controls (mean age = 16.9 years). Group comparisons of fiber density (FD) and bundle morphology were run on a fixel-wise, tract-wise, and global white matter (GWM) basis. We found that individuals with ASD had reduced FD, suggestive of decreased axonal count, in several major white matter tracts, including the corpus callosum (CC), bilateral inferior frontal-occipital fasciculus, right arcuate fasciculus, and right uncinate fasciculus, as well as a GWM reduction. Secondary analyses assessed associations with social impairment in participants with ASD, and showed that lower FD in the splenium of the CC was associated with greater social impairment. Our findings suggest that reduced FD could be the primary microstructural white matter abnormality in ASD.

Functional Connectivity of the Dorsal Attention Network Predicts Selective Attention in 4-7 year-old Girls.

Early childhood is a period of profound neural development and remodeling during which attention skills undergo rapid maturation. Attention networks have been extensively studied in the adult brain, yet relatively little is known about changes in early childhood, and their relation to cognitive development. We investigated the association between age and functional connectivity (FC) within the dorsal attention network (DAN) and the association between FC and attention skills in early childhood. Functional magnetic resonance imaging data was collected during passive viewing in 44 typically developing female children between 4 and 7 years whose sustained, selective, and executive attention skills were assessed. FC of the intraparietal sulcus (IPS) and the frontal eye fields (FEF) was computed across the entire brain and regressed against age. Age was positively associated with FC between core nodes of the DAN, the IPS and the FEF, and negatively associated with FC between the DAN and regions of the default-mode network. Further, controlling for age, FC between the IPS and FEF was significantly associated with selective attention. These findings add to our understanding of early childhood development of attention networks and suggest that greater FC within the DAN is associated with better selective attention skills.

Early identification of NORSE and transfer to care setting with appropriate supports: A proposed algorithm.

New-onset refractory status epilepticus (NORSE) is a clinical presentation where an individual develops refractory status epilepticus without active epilepsy, or related neurological conditions. A subset of these individuals has a preceding fever and would be diagnosed with febrile infection-related epilepsy syndrome (FIRES). The underlying etiology of this condition varies and includes autoimmune and viral encephalitides. These conditions require multiple specialized health care teams working collaboratively and specific resources for investigation of the underlying etiology and management to provide optimal patient care. In this paper, we provide: (1) recommendations upon early recognition of NORSE and FIRES, (2) guidance on the resources needed to optimally provide care, and (3) guidance on considerations to initiate transfer of patients to a more specialized medical center. Additional recommendations for resource-austere centers without the ability to transfer such patients are also discussed. These recommendations are only for adult patients with NORSE as pediatric patients may require additional special considerations.

Learning with individual-interest outcomes in Autism Spectrum Disorder.

Recent work has suggested atypical neural reward responses in individuals with Autism Spectrum Disorder (ASD), particularly for social reinforcers. Less is known about neural responses to restricted interests and few studies have investigated response to rewards in a learning context. We investigated neurophysiological differences in reinforcement learning between adolescents with ASD and typically developing (TD) adolescents (27 ASD, 31 TD). FMRI was acquired during a learning task in which participants chose one of two doors to reveal an image outcome. Doors differed in their probability of showing liked and not-liked images, which were individualized for each participant. Participants chose the door paired with liked images, but not the door paired with not-liked images, significantly above chance and choice allocation did not differ between groups. Interestingly, participants with ASD made choices less consistent with their initial door preferences. We found a neural prediction-error response at the time of outcome in the ventromedial prefrontal and posterior cingulate cortices that did not differ between groups. Together, behavioural and neural findings suggest that learning with individual interest outcomes is not different between individuals with and without ASD, adding to our understanding of motivational aspects of ASD.

Monoamine Oxidase A in Antisocial Personality Disorder and Borderline Personality Disorder.

PURPOSE OF REVIEW: Variation in the monoamine oxidase A (MAO-A) gene and MAO-A enzyme levels have been linked to antisocial behavior and aggression in clinical and non-clinical populations. Here, we provide an overview of the genetic, epigenetic, and neuroimaging research that has examined MAO-A structure and function in antisocial personality disorder (ASPD) and borderline personality disorder (BPD). RECENT FINDINGS: The low-activity MAO-A variable nucleotide tandem repeat genetic polymorphism has shown a robust association with large samples of violent and seriously violent offenders, many of whom had ASPD. A recent positron emission tomography (PET) study of ASPD similarly revealed low MAO-A density in brain regions thought to contribute to the psychopathology of the condition. By contrast, PET has also demonstrated that brain MAO-A levels are increased in BPD and that they relate to symptoms of low mood and suicidality. SUMMARY: Candidate gene studies have produced the most compelling evidence connecting MAO-A genetic variants to both ASPD and BPD. Still, conflicting results abound in the literature, making it highly unlikely that ASPD or BPD is related to a specific MAO-A genetic variant. Future research should strive to examine how MAO-A genotypes interact with broad-spectrum environmental influences to produce brain endophenotypes that may ultimately become tractable targets for novel treatment strategies.

Circumscribed interests in adolescents with Autism Spectrum Disorder: A look beyond trains, planes, and clocks.

Adolescence is a unique developmental period, characterized by physical and emotional growth and significant maturation of cognitive and social skills. For individuals with Autism Spectrum Disorder (ASD), it is also a vulnerable period as cognitive and social skills can deteriorate. Circumscribed interests (CIs), idiosyncratic areas of intense interest and focus, are a core symptom of ASD that may be associated with social development. Yet, relatively little is known about the expression of CIs in adolescents with ASD. Many studies investigating CIs have used images depicting items of special interest; however, it is not clear how images should be customized for adolescent studies. The goal of this study was to gain insight into the types of images that may be appropriate for studies of CIs in adolescents with ASD. To this end, we used a mixed methods design that included, 1) one-on-one interviews with 10 adolescents (4 with ASD and 6 TD), to identify categories of images that were High Autism Interest ('HAI') or High Typically Developing Interest ('HTD'), and 2) an online survey taken by fifty-three adolescents with ASD (42 male) and 135 typically developing (TD) adolescents (55 male) who rated how much they liked 105 'HAI' and 'HTD' images. Although we found a significant interaction between 'HAI' and 'HTD' categories and diagnosis, neither group significantly preferred one category over the other, and only one individual category ('Celebrities') showed a significant group effect, favored by TD adolescents. Males significantly preferred 'HAI' images relative to females, and TD adolescents significantly preferred images with social content relative to adolescents with ASD. Our findings suggest that studies investigating affective or neural responses to CI-related stimuli in adolescents should consider that stereotypical ASD interests (e.g. trains, gadgets) may not accurately represent individual adolescents with ASD, many of whom show interests that overlap with TD adolescents (e.g. video games).

Pre-ictal BOLD alterations: Two cases of patients with focal epilepsy.

The pre-ictal state is of interest for better understanding pathophysiological processes leading up to seizures and for identifying potential biomarkers for the prediction of these events. We present two cases of patients with focal epilepsy (occipital, insular) who had seizures during functional magnetic resonance imaging (fMRI) scans. Interictal (>30min pre-seizure) control data was available for one participant. The location and timing of pre-ictal blood oxygenation-level dependent (BOLD) signal alterations were examined along with changes in pre-ictal functional connectivity. BOLD signal increases were seen at/close to the seizure onset zone and in/near a contralateral homologous region for both patients. In one patient, BOLD signal decreases were also observed distant from the seizure onset zone. The BOLD signal changes began 11 to 3min prior to seizure onset. These findings add to a growing number of cases of pre-ictal hemodynamic alterations. The significant BOLD signal increases seen in/near the homologous region contralateral to the seizure onset zone in both patients suggests that this area may play a critical role in the pre-ictal state, perhaps functioning to inhibit the seizure onset zone, or alternatively, to be directly involved in seizure generation. Pre-ictal functional connectivity, using a seed at the presumed seizure onset zone, demonstrated increases in connectivity with regions near the contralateral homologous region prior to seizures. Alterations in connectivity were also observed and characterized in interictal data, highlighting the importance of future research in determining if the observed pre-ictal changes are specific indicators for impending seizures.

Variation in functional connectivity along anterior-to-posterior intraparietal sulcus, and relationship with age across late childhood and adolescence.

The intraparietal sulcus (IPS), a region in the dorsal attention network (DAN), has been implicated in multi-sensory attention and working memory. Working memory and attention develop across childhood; changes in functional connectivity within the DAN may relate to this maturation. Previous findings regarding fronto-parietal intrinsic functional connectivity age-effects were mixed. Our study aimed to circumvent limitations of previous work using a large cross-sectional sample, 183 typically developing participants 6.5-20 years, from the Autism Brain Imaging Data Exchange, and seed regions along the anterior-to-posterior axis of the IPS. These seeds, IPS0-4, were entered into functional connectivity models. Group-level models investigated differential connectivity along the IPS and relationships with age. Anterior IPS3/4 exhibited greater connectivity with sensorimotor/pre-motor regions. Posterior IPS0/1 demonstrated greater connectivity with dorsal and ventral visual regions. Positive age-effects were found between IPS3-4 and visual regions. Negative age-effects were found between IPS and superior parietal and medial orbitofrontal cortices. Follow-up region of interest analyses were used to estimate age-effects for DAN and anticorrelated default mode network regions. Results suggest age-effects on IPS functional connectivity are relatively modest, and may differ pre- and across-adolescence. Studying typical age-related connectivity variability within this network may help to understand neurodevelopmental disorders marked by impaired attention.

Artifact reduction in long-term monitoring of cerebral hemodynamics using near-infrared spectroscopy.

Near-infrared spectroscopy (NIRS) is a noninvasive neuroimaging technique used to assess cerebral hemodynamics. Its portability, ease of use, and relatively low operational cost lend itself well to the long-term monitoring of hemodynamic changes, such as those in epilepsy, where events are unpredictable. Long-term monitoring is associated with challenges including alterations in behaviors and motion that can result in artifacts. Five patients with epilepsy were assessed for interictal hemodynamic changes and alterations in behavior or motion. Based on this work, visual inspection was used to identify NIRS artifacts during a period of interest, specifically prior to seizures, in four patients. A motion artifact reduction algorithm (MARA, also known as the spline interpolation method) was tested on these data. Alterations in the NIRS measurements often occurred simultaneously with changes in motion and behavior. Occasionally, sharp shift artifacts were observed in the data. When artifacts appeared as sustained baseline shifts in the data, MARA reduced the standard deviation of the data and the appearance improved. We discussed motion and artifacts as challenges associated with long-term monitoring of cerebral hemodynamics in patients with epilepsy and our group's approach to circumvent these challenges and improve the quality of the data collected.

Theta-modulated gamma-band synchronization among activated regions during a verb generation task.

Expressive language is complex and involves processing within a distributed network of cortical regions. Functional MRI and magnetoencephalography (MEG) have identified brain areas critical for expressive language, but how these regions communicate across the network remains poorly understood. It is thought that synchronization of oscillations between neural populations, particularly at a gamma rate (>30 Hz), underlies functional integration within cortical networks. Modulation of gamma rhythms by theta-band oscillations (4-8 Hz) has been proposed as a mechanism for the integration of local cell coalitions into large-scale networks underlying cognition and perception. The present study tested the hypothesis that these oscillatory mechanisms of functional integration were present within the expressive language network. We recorded MEG while subjects performed a covert verb generation task. We localized activated cortical regions using beamformer analysis, calculated inter-regional phase locking between activated areas, and measured modulation of inter-regional gamma synchronization by theta phase. The results show task-dependent gamma-band synchronization among regions activated during the performance of the verb generation task, and we provide evidence that these transient and periodic instances of high-frequency connectivity were modulated by the phase of cortical theta oscillations. These findings suggest that oscillatory synchronization and cross-frequency interactions are mechanisms for functional integration among distributed brain areas supporting expressive language processing.