The origin, structure, and function of the claustrum, as well as its role in neural computation, have remained a mystery since its discovery in the 17th century. Assessing the in vivo connectivity of the claustrum may bring forth useful insights with relevance to models the overall functionality of the claustrum itself. Using structural and diffusion tensor neuroimaging in N=100 healthy subjects, we found that the claustrum has the highest connectivity in the brain by regional volume. Network theoretical analyses revealed that a) the claustrum is a primary contributor to global brain network architecture, and that b) significant connectivity dependencies exist between the claustrum, frontal lobe, and cingulate regions. These results illustrate that the claustrum is ideally located within the human CNS connectome to serve as the putative “gate keeper” of neural information for consciousness awareness. Our findings support and underscore prior theoretical contributions about the involvement of the claustrum in higher cognitive function and its relevance in devastating neurological disease.

IMPORTANCE Impaired mitochondrial function impacts many biological processes that depend heavily on energy and metabolism and can lead to a wide range of neurodevelopmental disorders, including autism spectrum disorder (ASD). Although evidence that mitochondrial dysfunction is a biological subtype of ASD has grown in recent years, no study, to our knowledge, has demonstrated evidence of mitochondrial dysfunction in brain tissue in vivo in a large, well-defined sample of individuals with ASD.OBJECTIVES To assess brain lactate in individuals with ASD and typically developing controls using high-resolution, multiplanar spectroscopic imaging; to map the distribution of lactate in the brains of individuals with ASD; and to assess correlations of elevated brain lactate with age, autism subtype, and intellectual ability.

ObjectiveNo drug is yet approved to treat the core symptoms of autism spectrum disorder (ASD). Low‐dose suramin was effective in the maternal immune activation and Fragile X mouse models of ASD. The Suramin Autism Treatment‐1 (SAT‐1) trial was a double‐blind, placebo‐controlled, translational pilot study to examine the safety and activity of low‐dose suramin in children with ASD.MethodsTen male subjects with ASD, ages 5–14 years, were matched by age, IQ, and autism severity into five pairs, then randomized to receive a single, intravenous infusion of suramin (20 mg/kg) or saline. The primary outcomes were ADOS‐2 comparison scores and Expressive One‐Word Picture Vocabulary Test (EOWPVT). Secondary outcomes were the aberrant behavior checklist, autism treatment evaluation checklist, repetitive behavior questionnaire, and clinical global impression questionnaire.ResultsBlood levels of suramin were 12 ± 1.5 μmol/L (mean ± SD) at 2 days and 1.5 ± 0.5 μmol/L after 6 weeks. The terminal half‐life was 14.7 ± 0.7 days. A self‐limited, asymptomatic rash was seen, but there were no serious adverse events. ADOS‐2 comparison scores improved by −1.6 ± 0.55 points (n = 5; 95% CI = −2.3 to −0.9; Cohen's d = 2.9; P = 0.0028) in the suramin group and did not change in the placebo group. EOWPVT scores did not change. Secondary outcomes also showed improvements in language, social interaction, and decreased restricted or repetitive behaviors.InterpretationThe safety and activity of low‐dose suramin showed promise as a novel approach to treatment of ASD in this small study.

ASD Autism spectrum disorders MNS Mirror neuron system STS Superior temporal sulcus AIM The aim of this article is to review neuroimaging studies of autism spectrum disorders (ASD) that examine declarative, socio-emotional, and procedural learning and memory systems.METHOD We conducted a search of PubMed from 1996 to 2010 using the terms 'autism,' 'learning,' 'memory,' and 'neuroimaging.' We limited our review to studies correlating learning and memory function with neuroimaging features of the brain. RESULTSThe early literature supports the following preliminary hypotheses: (1) abnormalities of hippocampal subregions may contribute to autistic deficits in episodic and relational memory; (2) disturbances to an amygdala-based network (which may include the fusiform gyrus, superior temporal cortex, and mirror neuron system) may contribute to autistic deficits in socio-emotional learning and memory; and (3) abnormalities of the striatum may contribute to developmental dyspraxia in individuals with ASD.INTERPRETATION Characterizing the disturbances to learning and memory systems in ASD can inform our understanding of the neural bases of autistic behaviors and the phenotypic heterogeneity of ASD.In 1943, Leo Kanner 1 published his seminal manuscript describing a group of children with a 'powerful desire for aloneness and sameness.' The key themes identified by Kanner have since been refined into a set of three nosological criteria that serve as the criterion standard for diagnosing autism spectrum disorders (ASD): disturbances in (1) social interaction, (2) communication, and (3) behavioral flexibility. How these different phenomenological criteria 'map' onto the brain has been a topic of intense investigation in recent years, with over 300 neuroimaging studies of ASD published in the past three decades.Although the neural bases of the individual features of the autistic triad have yet to be clearly defined, neuroimaging studies have provided key insights into the brain disturbances present in individuals with ASD. Perhaps the most important discovery has been a trajectory of early brain overgrowth within the first years of life followed by premature growth arrest.2 This aberrant growth occurs at a critical time in human brain development, during which synaptogenesis, neuronal growth and differentiation, and myelination establish networks of local and long-range connections that are essential for normal cognitive and behavioral development. Neuroimaging studies have also identified several neural systems of interest that may be associated with certain autistic behaviors. Deficits in certain social behaviors, for example, have been associated in some studies with abnormalities of the amygdala, mirror neuron system (MNS), and superior temporal gyrus, whereas stereotyped repetitive behaviors have been associated with abnormalities of the striatum. 3,4 Neuroimaging studies of ASD, however, face a number of limitations. Abnormalities of brain function are known to be present in early infancy in ASD, long before most imagi...

Background: Our aim was to assess resting cerebral blood flow (rCBF) in children and adults with Autism Spectrum Disorder (ASD). Methods: We acquired pulsed arterial spin labeling MRI data in 44 generally high functioning ASD simplex participants and 66 typically developing (TD) controls with comparable mean fullscale IQ's. We compared rCBF values voxel-wise across diagnostic groups and assessed correlations with symptom scores. We also assessed the moderating influences of participant age, sex, and IQ on our findings and the correlations of rCBF with NAA (N-acetylaspartate) metabolite levels. Results: We detected significantly higher rCBF values throughout frontal white matter and subcortical gray in ASD participants. rCBF correlated positively with socialization deficits in regions where ASD hyperperfusion was greatest. rCBF declined with increasing IQ in the TD group, a correlation that was absent in ASD participants because their rCBF values were elevated across all IQ levels. rCBF in the ASD group correlated inversely with NAA metabolite levels throughout frontal white matter, with greater rCBF accompanying lower and increasingly abnormal NAA levels relative to TD controls. Conclusions: These findings taken together suggest the presence of altered metabolism, likely of mitochondrial origin, and dysfunctional maintenance processes that support axonal functioning in ASD. These disturbances in turn likely reduce neural efficiency for cognitive and social