Recent studies of autism have identified functional abnormalities of the default network during a passive resting state. Since the default network is also typically engaged during social, emotional ...and introspective processing, dysfunction of this network may underlie some of the difficulties individuals with autism exhibit in these broad domains. In the present experiment, we attempted to further delineate the nature of default network abnormality in autism using experimentally constrained social and introspective tasks. Thirteen autism and 12 control participants were scanned while making true/false judgments for various statements about themselves (SELF condition) or a close other person (OTHER), and pertaining to either psychological personality traits (INTERNAL) or observable characteristics and behaviors (EXTERNAL). In the ventral medial prefrontal cortex/ventral anterior cingulate cortex, activity was reduced in the autism group across all judgment conditions and also during a resting condition, suggestive of task-independent dysfunction of this region. In other default network regions, overall levels of activity were not different between groups. Furthermore, in several of these regions, we found group by condition interactions only for INTERNAL/EXTERNAL judgments, and not SELF/OTHER judgments, suggestive of task-specific dysfunction. Overall, these results provide a more detailed view of default network functionality and abnormality in autism.
A leading hypothesis for the neural basis of autism postulates globally abnormal brain connectivity, yet the majority of studies report effects that are either very weak, inconsistent across studies, ...or explain results incompletely. Here we apply multiple analytical approaches to resting-state BOLD-fMRI data at the whole-brain level. Neurotypical and high-functioning adults with autism displayed very similar patterns and strengths of resting-state connectivity. We found only limited evidence in autism for abnormal resting-state connectivity at the regional level and no evidence for altered connectivity at the whole-brain level. Regional abnormalities in functional connectivity in autism spectrum disorder were primarily in the frontal and temporal cortices. Within these regions, functional connectivity with other brain regions was almost exclusively lower in the autism group. Further examination showed that even small amounts of head motion during scanning have large effects on functional connectivity measures and must be controlled carefully. Consequently, we suggest caution in the interpretation of apparent positive findings until all possible confounding effects can be ruled out. Additionally, we do not rule out the possibility that abnormal connectivity in autism is evident at the microstructural synaptic level, which may not be reflected sensitively in hemodynamic changes measured with BOLD-fMRI.
Objective. To assess the effects of a computer-free classroom on first-year Doctor of Pharmacy (PharmD) students’ performance in a pathophysiology course.
Methods. In the 2018 course offering, the ...instructor enforced an electronics-free classroom where students could not access computers to take notes during lectures. Data were compared to a previous iteration of the course in which students could use computers for notetaking if they desired. Four in-class examinations were given by the instructor and performance between the two student classes were compared.
Results. The average examination grade increased 3% in the electronics-free classroom. Overall, final course grades were similar for students receiving A’s and B’s, but there was a notable increase in C’s and a corresponding decrease in course failures. Course evaluations remained consistent and a slight majority of student comments were supportive of the computer-free environment.
Conclusion. Student performance on examinations and in the course improved within the electronics-free classroom, especially for students at the lower end of the grading scale. This work provides important insights for faculty and administrators as they weigh whether to create a computer-free learning environment.
Temporal correlations between different brain regions in the resting-state BOLD signal are thought to reflect intrinsic functional brain connectivity (Biswal et al., 1995; Greicius et al., 2003; Fox ...et al., 2007). The functional networks identified are typically bilaterally distributed across the cerebral hemispheres, show similarity to known white matter connections (Greicius et al., 2009), and are seen even in anesthetized monkeys (Vincent et al., 2007). Yet it remains unclear how they arise. Here we tested two distinct possibilities: (1) functional networks arise largely from structural connectivity constraints, and generally require direct interactions between functionally coupled regions mediated by white-matter tracts; and (2) functional networks emerge flexibly with the development of normal cognition and behavior and can be realized in multiple structural architectures. We conducted resting-state fMRI in eight adult humans with complete agenesis of the corpus callosum (AgCC) and normal intelligence, and compared their data to those from eight healthy matched controls. We performed three main analyses: anatomical region-of-interest-based correlations to test homotopic functional connectivity, independent component analysis (ICA) to reveal functional networks with a data-driven approach, and ICA-based interhemispheric correlation analysis. Both groups showed equivalently strong homotopic BOLD correlation. Surprisingly, almost all of the group-level independent components identified in controls were observed in AgCC and were predominantly bilaterally symmetric. The results argue that a normal complement of resting-state networks and intact functional coupling between the hemispheres can emerge in the absence of the corpus callosum, favoring the second over the first possibility listed above.
Although the neurobiology of autism has been studied for more than two decades, the majority of these studies have examined brain structure 10, 20, or more years after the onset of clinical symptoms. ...The pathological biology that causes autism remains unknown, but its signature is likely to be most evident during the first years of life when clinical symptoms are emerging. This review highlights neurobiological findings during the first years of life and emphasizes early brain overgrowth as a key factor in the pathobiology of autism. We speculate that excess neuron numbers may be one possible cause of early brain overgrowth and produce defects in neural patterning and wiring, with exuberant local and short-distance cortical interactions impeding the function of large-scale, long-distance interactions between brain regions. Because large-scale networks underlie socio-emotional and communication functions, such alterations in brain architecture could relate to the early clinical manifestations of autism. As such, autism may additionally provide unique insight into genetic and developmental processes that shape early neural wiring patterns and make possible higher-order social, emotional, and communication functions.
Abstract
Objectives
The current study explores whether personal social network characteristics are associated with older adults’ memory and/or social cognitive function (e.g., ability to infer ...other’s mental states—theory of mind).
Method
120 older adults completed a social network interview, a memory measure, and 2 core measures of social cognitive functions: emotion recognition and theory of mind.
Results
Variation in memory and social cognitive abilities predicted distinct aspects of older adults’ social networks. Having better memory predicted having larger, less-dense social networks, but better theory of mind was associated with having at least one acquaintance in the network, and having more heterogeneous social relationships within the network.
Discussion
Together our findings suggest that disparate social cognitive abilities may serve unique functions, facilitating maintenance of beneficial social connections.
Peer-grouping is used in many sectors for organisational learning, policy implementation, and benchmarking. Clustering provides a statistical, data-driven method for constructing meaningful peer ...groups, but peer groups must be compatible with business constraints such as size and stability considerations. Additionally, statistical peer groups are constructed from many different variables, and can be difficult to understand, especially for non-statistical audiences. We developed methodology to apply business constraints to clustering solutions and allow the decision-maker to choose the balance between statistical goodness-of-fit and conformity to business constraints. Several tools were utilised to identify complex distinguishing features in peer groups, and a number of visualisations are developed to explain high-dimensional clusters for non-statistical audiences. In a case study where peer group size was required to be small (less than or equal to 100 members), we applied constrained clustering to a noisy high-dimensional data-set over two subsequent years, ensuring that the clusters were sufficiently stable between years. Our approach not only satisfied clustering constraints on the test data, but maintained an almost monotonic negative relationship between goodness-of-fit and stability between subsequent years. We demonstrated in the context of the case study how distinguishing features between clusters can be communicated clearly to different stakeholders with substantial and limited statistical knowledge.
The ability to discern the target of another person's gaze is critical for social and linguistic development, but functions atypically in autism spectrum disorder (ASD). A multi-pronged approach ...allowed us to deconstruct this complex ability, to uncover the fundamental bases of this impairment. We analyzed performance on a novel gaze perception task with classical psychophysical metrics (precision and accuracy), principal component analysis (in the analysis of spatial biases), and Bayesian computational modeling (in the analysis of individual subjects' use of contextual salience cues). Compared to controls, adults with ASD were less precise and less accurate in their judgments of gaze direction. Further, although nearly all controls exhibited a prototypical pattern of spatial bias in their judgments, this spatial prior was severely disrupted among a large subset of ASD participants. By contrast, Bayesian computational modeling revealed that both groups exploited contextual salience cues in their gaze judgments, and that the average strength of this contextual prior was similar for both groups. This comprehensive study revealed that although most ASD participants performed atypically in at least one aspect of gaze perception, the particular aspects disrupted varied idiosyncratically across individuals. Impairment in gaze perception in ASD likely arises via heterogeneous underlying mechanisms.
Extracellular protein disulfide isomerase (PDI) is required for platelet thrombus formation and fibrin generation after arteriolar wall injury in live mice. PDI is secreted from platelets and ...endothelial cells on cellular activation, but the mechanism of capture of secreted PDI within the injured vasculature is unknown. We establish that, like the endothelial β3 integrin αVβ3, the platelet integrin αIIbβ3 binds PDI. PDI also binds to recombinant β3. Using intravital microscopy, we demonstrate that PDI accumulation at the site of laser-induced arteriolar wall injury is markedly reduced in β3-null (β3−/−) mice, and neither a platelet thrombus nor fibrin is generated at the vessel injury site. The absence of fibrin after vascular injury in β3−/− mice is because of the absence of extracellular PDI. To evaluate the relative importance of endothelial αVβ3 versus platelet αIIbβ3 or αVβ3, we performed reciprocal bone marrow transplants on wild-type and β3−/− mice. PDI accumulation and platelet thrombus formation were markedly decreased after vessel injury in wild-type mice transplanted with β3−/− bone marrow or in β3−/− mice transplanted with wild-type bone marrow. These results indicate that both endothelial and platelet β3 integrins contribute to extracellular PDI binding at the vascular injury site.
Objective. To incorporate active-learning sessions into a lecture-based pharmacology course, assess the impact on student learning and attitudes, and address commonly perceived barriers to ...implementing active learning. Methods. Prior to the redesign, the course met twice a week for 75 minutes. As part of the redesign, the two weekly lecture sessions were reduced to 50 minutes each. Additionally, students were assigned to one of three sections that met separately once a week for a 50-minute recitation session in which they applied course concepts to cases, problems, and situations. Data from the two years before the redesign and two years after it were assessed. Results. Students' average course grade increased 2.5% after the redesign. Average ratings of the course and instructor on student evaluations each increased significantly (around 0.3 points on a 5-point scale). Conclusion. Student knowledge and performance in a pharmacology course increased when a portion of the time previously devoted to lecture was replaced with an active-learning session. This experience can serve as a blueprint for how to convert a lecture-only course into a hybrid lecture and recitation model.
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