The neural and cognitive basis of expository text comprehension.

As science and technology rapidly progress, it becomes increasingly important to understand how individuals comprehend expository technical texts that explain these advances. This study examined differences in individual readers' technical comprehension performance and differences among texts, using functional brain imaging to measure regional brain activity while students read passages on technical topics and then took a comprehension test. Better comprehension of the technical passages was related to higher activation in regions of the left inferior frontal gyrus, left superior parietal lobe, bilateral dorsolateral prefrontal cortex, and bilateral hippocampus. These areas are associated with the construction of a mental model of the passage and with the integration of new and prior knowledge in memory. Poorer comprehension of the passages was related to greater activation of the ventromedial prefrontal cortex and the precuneus, areas involved in autobiographical and episodic memory retrieval. More comprehensible passages elicited more brain activation associated with establishing links among different types of information in the text and activation associated with establishing conceptual coherence within the text representation. These findings converge with previous behavioral research in their implications for teaching technical learners to become better comprehenders and for improving the structure of instructional texts, to facilitate scientific and technological comprehension.

Rapid neuroplasticity changes and response to intravenous ketamine: a randomized controlled trial in treatment-resistant depression.

Intravenous ketamine is posited to rapidly reverse depression by rapidly enhancing neuroplasticity. In human patients, we quantified gray matter microstructural changes on a rapid (24-h) timescale within key regions where neuroplasticity enhancements post-ketamine have been implicated in animal models. In this study, 98 unipolar depressed adults who failed at least one antidepressant medication were randomized 2:1 to a single infusion of intravenous ketamine (0.5 mg/kg) or vehicle (saline) and completed diffusion tensor imaging (DTI) assessments at pre-infusion baseline and 24-h post-infusion. DTI mean diffusivity (DTI-MD), a putative marker of microstructural neuroplasticity in gray matter, was calculated for 7 regions of interest (left and right BA10, amygdala, and hippocampus; and ventral Anterior Cingulate Cortex) and compared to clinical response measured with the Montgomery-Asberg Depression Rating Scale (MADRS) and the Quick Inventory of Depressive Symptoms-Self-Report (QIDS-SR). Individual differences in DTI-MD change (greater decrease from baseline to 24-h post-infusion, indicative of more neuroplasticity enhancement) were associated with larger improvements in depression scores across several regions. In the left BA10 and left amygdala, these relationships were driven primarily by the ketamine group (group * DTI-MD interaction effects: p = 0.016-0.082). In the right BA10, these associations generalized to both infusion arms (p = 0.007). In the left and right hippocampus, on the MADRS only, interaction effects were observed in the opposite direction, such that DTI-MD change was inversely associated with depression change in the ketamine arm specifically (group * DTI-MD interaction effects: p = 0.032-0.06). The acute effects of ketamine on depression may be mediated, in part, by acute changes in neuroplasticity quantifiable with DTI.

Reduced White Matter Integrity and Deficits in Neuropsychological Functioning in Adults With Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is currently viewed as a disorder of cortical systems connectivity, with a heavy emphasis being on the structural integrity of white matter tracts. However, the majority of the literature to date has focused on children with ASD. Understanding the integrity of white matter tracts in adults may help reveal the nature of ASD pathology in adulthood and the potential contributors to cognitive impairment. This study examined white matter water diffusion using diffusion tensor imaging in relation to neuropsychological measures of cognition in a sample of 45 adults with ASD compared to 20 age, gender, and full-scale-IQ-matched healthy volunteers. Tract-based spatial statistics were used to assess differences in diffusion along white matter tracts between groups using permutation testing. The following neuropsychological measures of cognition were assessed: processing speed, attention vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. Results indicated that fractional anisotropy (FA) was significantly reduced in adults with ASD in the anterior thalamic radiation (P = 0.022) and the right cingulum (P = 0.008). All neuropsychological measures were worse in the ASD group, but none of the measures significantly correlated with reduced FA in either tract in the adults with ASD or in the healthy volunteers. Together, this indicates that the tracts that are the most impacted in autism may not be (at least directly) responsible for the behavioral deficits in ASD. Autism Res 2020, 13: 702-714. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: White matter tracts are the data cables in the brain that efficiently transfer information, and damage to these tracts could be the cause for the abnormal behaviors that are associated with autism. We found that two long-range tracts (the anterior thalamic radiation and the cingulum) were both impaired in autism but were not directly related to the impairments in behavior. This suggests that the abnormal tracts and behavior are the effects of another underlying mechanism.

Converging measures of neural change at the microstructural, informational, and cortical network levels in the hippocampus during the learning of the structure of organic compounds.

The critical role of the hippocampus in human learning has been illuminated by neuroimaging studies that increasingly improve the detail with which hippocampal function is understood. However, the hippocampal information developed with different types of imaging technologies is seldom integrated within a single investigation of the neural changes that occur during learning. Here, we show three different ways in which a small hippocampal region changes as the structures and names of a set of organic compounds are being learned, reflecting changes at the microstructural, informational, and cortical network levels. The microstructural changes are sensed using measures of water diffusivity. The informational changes are assessed using machine learning of the neural representations of organic compounds as they are encoded in the fMRI-measured activation levels of a set of hippocampal voxels. The changes in cortical networks are measured in terms of the functional connectivity between hippocampus and parietal regions. The co-location of these three hippocampal changes reflects that structure's involvement in learning at all three levels of explanation, consistent with the multiple ways in which learning brings about neural change.

Alterations of functional connectivity and intrinsic activity within the cingulate cortex of suicidal ideators.

The 'default mode network' (DMN), a collection of brain regions including the posterior cingulate cortex (PCC), shows reliable inter-regional functional connectivity at rest. It has been implicated in rumination and other negative affective states, but its role in suicidal ideation is not well understood. We employed seed based functional connectivity methods to analyze resting state fMRI data in 34 suicidal ideators and 40 healthy control participants. Whole-brain connectivity with dorsal PCC or ventral PCC was broadly intact between the two groups, but while the control participants showed greater coupling between the dorsal anterior cingulate cortex (dACC) and dorsal PCC, compared to the dACC and ventral PCC, this difference was reversed in the ideators. Furthermore, ongoing low frequency BOLD signal in these three regions (dorsal, ventral PCC, dACC) was reduced in the ideators. The structural integrity of the cingulum bundle, as measured using diffusion tensor imaging (DTI), also explained variation in the functional connectivity measures but did not abolish the group differences. Together, these findings provide evidence of abnormalities in the DMN underlying the tendency towards suicidal ideation.

Structural and functional neuroplasticity in human learning of spatial routes.

Recent findings with both animals and humans suggest that decreases in microscopic movements of water in the hippocampus reflect short-term neuroplasticity resulting from learning. Here we examine whether such neuroplastic structural changes concurrently alter the functional connectivity between hippocampus and other regions involved in learning. We collected both diffusion-weighted images and fMRI data before and after humans performed a 45min spatial route-learning task. Relative to a control group with equal practice time, there was decreased diffusivity in the posterior-dorsal dentate gyrus of the left hippocampus in the route-learning group accompanied by increased synchronization of fMRI-measured BOLD signal between this region and cortical areas, and by changes in behavioral performance. These concurrent changes characterize the multidimensionality of neuroplasticity as it enables human spatial learning.

Aberrant functioning of the theory-of-mind network in children and adolescents with autism.

BACKGROUND: Theory-of-mind (ToM), the ability to infer people's thoughts and feelings, is a pivotal skill in effective social interactions. Individuals with autism spectrum disorders (ASD) have been found to have altered ToM skills, which significantly impacts the quality of their social interactions. Neuroimaging studies have reported altered activation of the ToM cortical network, especially in adults with autism, yet little is known about the brain responses underlying ToM in younger individuals with ASD. This functional magnetic resonance imaging (fMRI) study investigated the neural mechanisms underlying ToM in high-functioning children and adolescents with ASD and matched typically developing (TD) peers. METHODS: fMRI data were acquired from 13 participants with ASD and 13 TD control participants while they watched animations involving two "interacting" geometrical shapes. RESULTS: Participants with ASD showed significantly reduced activation, relative to TD controls, in regions considered part of the ToM network, the mirror network, and the cerebellum. Functional connectivity analyses revealed underconnectivity between frontal and posterior regions during task performance in the ASD participants. CONCLUSIONS: Overall, the findings of this study reveal disruptions in the brain circuitry underlying ToM in ASD at multiple levels, including decreased activation and decreased functional connectivity.

Identifying autism from neural representations of social interactions: neurocognitive markers of autism.

Autism is a psychiatric/neurological condition in which alterations in social interaction (among other symptoms) are diagnosed by behavioral psychiatric methods. The main goal of this study was to determine how the neural representations and meanings of social concepts (such as to insult) are altered in autism. A second goal was to determine whether these alterations can serve as neurocognitive markers of autism. The approach is based on previous advances in fMRI analysis methods that permit (a) the identification of a concept, such as the thought of a physical object, from its fMRI pattern, and (b) the ability to assess the semantic content of a concept from its fMRI pattern. These factor analysis and machine learning methods were applied to the fMRI activation patterns of 17 adults with high-functioning autism and matched controls, scanned while thinking about 16 social interactions. One prominent neural representation factor that emerged (manifested mainly in posterior midline regions) was related to self-representation, but this factor was present only for the control participants, and was near-absent in the autism group. Moreover, machine learning algorithms classified individuals as autistic or control with 97% accuracy from their fMRI neurocognitive markers. The findings suggest that psychiatric alterations of thought can begin to be biologically understood by assessing the form and content of the altered thought's underlying brain activation patterns.

Modulation of cortical activity during comprehension of familiar and unfamiliar text topics in speed reading and speed listening.

Brain activation associated with normal and speeded comprehension of expository texts on familiar and unfamiliar topics was investigated in reading and listening. The goal was to determine how brain activation and the comprehension processes it reflects are modulated by comprehension speed and topic familiarity. Passages on more familiar topics differentially activated a set of areas in the anterior temporal lobe and medial frontal gyrus, areas often associated with text-level integration processes, which we interpret to reflect integration of previous knowledge with the passage content. Passages presented at the faster presentation resulted in more activation of a network of frontal areas associated with strategic and working-memory processes (as well as visual or auditory sensory-related regions), which we interpret to reflect maintenance of local coherence among briefly available passage segments. The implications of this research is that the brain system for text comprehension adapts to varying perceptual and knowledge conditions.

The local, global, and neural aspects of visuospatial processing in autism spectrum disorders.

Behavioral studies have documented a relative advantage in some aspects of visuospatial cognition in autism although it is not consistently found in higher functioning individuals with autism. The purpose of this functional neuroimaging study was to examine the neural activity in high functioning individuals with autism while they performed a block design task that systematically varied with regard to whether a global pattern was present. Participants were 14 adults with high-functioning autism and 14 age and IQ matched typical controls. The task was to identify a missing block in target figures which had either an obvious global shape or was an arbitrary array of blocks. Behavioral results showed intact, but not superior, performance in our participants with autism. A key group difference was that the participants with autism showed reliably greater activation in occipital and parietal regions in both tasks suggesting an increased reliance of the autism group on posterior brain areas to mediate visuospatial tasks. Thus, increased reliance on relatively posterior brain regions in itself may not guarantee superior performance as seen in the present study.

Brain function differences in language processing in children and adults with autism.

Comparison of brain function between children and adults with autism provides an understanding of the effects of the disorder and associated maturational differences on language processing. Functional imaging (functional magnetic resonance imaging) was used to examine brain activation and cortical synchronization during the processing of literal and ironic texts in 15 children with autism, 14 children with typical development, 13 adults with autism, and 12 adult controls. Both the children and adults with autism had lower functional connectivity (synchronization of brain activity among activated areas) than their age and ability comparison group in the left hemisphere language network during irony processing, and neither autism group had an increase in functional connectivity in response to increased task demands. Activation differences for the literal and irony conditions occurred in key language-processing regions (left middle temporal, left pars triangularis, left pars opercularis, left medial frontal, and right middle temporal). The children and adults with autism differed from each other in the use of some brain regions during the irony task, with the adults with autism having activation levels similar to those of the control groups. Overall, the children and adults with autism differed from the adult and child controls in (a) the degree of network coordination, (b) the distribution of the workload among member nodes, and (3) the dynamic recruitment of regions in response to text content. Moreover, the differences between the two autism age groups may be indicative of positive changes in the neural function related to language processing associated with maturation and/or educational experience.

Autism as a neural systems disorder: a theory of frontal-posterior underconnectivity.

The underconnectivity theory of autism attributes the disorder to lower anatomical and functional systems connectivity between frontal and more posterior cortical processing. Here we review evidence for the theory and present a computational model of an executive functioning task (Tower of London) implementing the assumptions of underconnectivity. We make two modifications to a previous computational account of performance and brain activity in typical individuals in the Tower of London task (Newman et al., 2003): (1) the communication bandwidth between frontal and parietal areas was decreased and (2) the posterior centers were endowed with more executive capability (i.e., more autonomy, an adaptation is proposed to arise in response to the lowered frontal-posterior bandwidth). The autism model succeeds in matching the lower frontal-posterior functional connectivity (lower synchronization of activation) seen in fMRI data, as well as providing insight into behavioral response time results. The theory provides a unified account of how a neural dysfunction can produce a neural systems disorder and a psychological disorder with the widespread and diverse symptoms of autism.

Distinctive neural processes during learning in autism.

This functional magnetic resonance imaging study compared the neural activation patterns of 18 high-functioning individuals with autism and 18 IQ-matched neurotypical control participants as they learned to perform a social judgment task. Participants learned to identify liars among pairs of computer-animated avatars uttering the same sentence but with different facial and vocal expressions, namely those that have previously been associated with lying versus truth-telling. Despite showing a behavioral learning effect similar to the control group, the autism group did not show the same pattern of decreased activation in cortical association areas as they learned the task. Furthermore, the autism group showed a significantly smaller increase in interregion synchronization of activation (functional connectivity) with learning than did the control group. Finally, the autism group had decreased structural connectivity as measured by corpus callosum size, and this measure was reliably related to functional connectivity measures. The findings suggest that cortical underconnectivity in autism may constrain the ability of the brain to rapidly adapt during learning.

Brain activation for language dual-tasking: listening to two people speak at the same time and a change in network timing.

The study used fMRI to investigate brain activation in participants who were able to listen to and successfully comprehend two people speaking at the same time (dual-tasking). The study identified brain mechanisms associated with high-level, concurrent dual-tasking, as compared with comprehending a single message. Results showed an increase in the functional connectivity among areas of the language network in the dual task. The increase in synchronization of brain activation for dual-tasking was brought about primarily by a change in the timing of left inferior frontal gyrus (LIFG) activation relative to posterior temporal activation, bringing the LIFG activation into closer correspondence with temporal activation. The results show that the change in LIFG timing was greater in participants with lower working memory capacity, and that recruitment of additional activation in the dual-task occurred only in the areas adjacent to the language network that was activated in the single task. The shift in LIFG activation may be a brain marker of how the brain adapts to high-level dual-tasking.

The neural basis of deictic shifting in linguistic perspective-taking in high-functioning autism.

Personal pronouns, such as 'I' and 'you', require a speaker/listener to continuously re-map their reciprocal relation to their referent, depending on who is saying the pronoun. This process, called 'deictic shifting', may underlie the incorrect production of these pronouns, or 'pronoun reversals', such as referring to oneself with the pronoun 'you', which has been reported in children with autism. The underlying neural basis of deictic shifting, however, is not understood, nor has the processing of pronouns been studied in adults with autism. The present study compared the brain activation pattern and functional connectivity (synchronization of activation across brain areas) of adults with high-functioning autism and control participants using functional magnetic resonance imaging in a linguistic perspective-taking task that required deictic shifting. The results revealed significantly diminished frontal (right anterior insula) to posterior (precuneus) functional connectivity during deictic shifting in the autism group, as well as reliably slower and less accurate behavioural responses. A comparison of two types of deictic shifting revealed that the functional connectivity between the right anterior insula and precuneus was lower in autism while answering a question that contained the pronoun 'you', querying something about the participant's view, but not when answering a query about someone else's view. In addition to the functional connectivity between the right anterior insula and precuneus being lower in autism, activation in each region was atypical, suggesting over reliance on individual regions as a potential compensation for the lower level of collaborative interregional processing. These findings indicate that deictic shifting constitutes a challenge for adults with high-functioning autism, particularly when reference to one's self is involved, and that the functional collaboration of two critical nodes, right anterior insula and precuneus, may play a critical role for deictic shifting by supporting an attention shift between oneself and others.

Inter-regional brain communication and its disturbance in autism.

In this review article, we summarize recent progress toward understanding disturbances in functional and anatomical brain connectivity in autism. Autism is a neurodevelopmental disorder affecting language, social interaction, and repetitive behaviors. Recent studies have suggested that limitations of frontal-posterior brain connectivity in autism underlie the varied set of deficits associated with this disorder. Specifically, the underconnectivity theory of autism postulates that individuals with autism have a reduced communication bandwidth between frontal and posterior cortical areas, which constrains the psychological processes that rely on the integrated functioning of frontal and posterior brain networks. This review summarizes the recent findings of reduced frontal-posterior functional connectivity (synchronization) in autism in a wide variety of high-level tasks, focusing on data from functional magnetic resonance imaging studies. It also summarizes the findings of disordered anatomical connectivity in autism, as measured by a variety of techniques, including distribution of white matter volumes and diffusion tensor imaging. We conclude with a discussion of the implications of these findings for autism and future directions for this line of research.

Cortical underconnectivity coupled with preserved visuospatial cognition in autism: Evidence from an fMRI study of an embedded figures task.

Individuals with high-functioning autism sometimes exhibit intact or superior performance on visuospatial tasks, in contrast to impaired functioning in other domains such as language comprehension, executive tasks, and social functions. The goal of the current study was to investigate the neural bases of preserved visuospatial processing in high-functioning autism from the perspective of the cortical underconnectivity theory. We used a combination of behavioral, functional magnetic resonance imaging, functional connectivity, and corpus callosum morphometric methodological tools. Thirteen participants with high-functioning autism and 13 controls (age-, IQ-, and gender-matched) were scanned while performing an Embedded Figures Task. Despite the ability of the autism group to attain behavioral performance comparable to the control group, the brain imaging results revealed several group differences consistent with the cortical underconnectivity account of autism. First, relative to controls, the autism group showed less activation in the left dorsolateral prefrontal and inferior parietal areas and more activation in visuospatial (bilateral superior parietal extending to inferior parietal and right occipital) areas. Second, the autism group demonstrated lower functional connectivity between higher-order working memory/executive areas and visuospatial regions (between frontal and parietal-occipital). Third, the size of the corpus callosum (an index of anatomical connectivity) was positively correlated with frontal-posterior (parietal and occipital) functional connectivity in the autism group. Thus, even in the visuospatial domain, where preserved performance among people with autism is observed, the neuroimaging signatures of cortical underconnectivity persist.

The nature of brain dysfunction in autism: functional brain imaging studies.

PURPOSE OF REVIEW: Functional magnetic resonance imaging studies have had a profound impact on the delineation of the neurobiologic basis for autism. Advances in fMRI technology for investigating functional connectivity, resting state connectivity, and a default mode network have provided further detail about disturbances in brain organization and brain-behavior relationships in autism to be reviewed in this article. RECENT FINDINGS: Recent fMRI studies have provided evidence of enhanced activation and connectivity of posterior, or parietal-occipital, networks and enhanced reliance on visuospatial abilities for visual and verbal reasoning in high functioning individuals with autism. Evidence also indicates altered activation in frontostriatal networks for cognitive control, particularly involving anterior cingulate cortex, and altered connectivity in the resting state and the default mode network. The findings suggest that the specialization of many cortical networks of the human brain has failed to develop fully in high functioning individuals with autism. SUMMARY: This research provides a growing specification of to the neurobiologic basis for this complex syndrome and for the co-occurrence of the signs and symptoms as a syndrome. With this knowledge has come new neurobiologically based opportunities for intervention.

Altering cortical connectivity: remediation-induced changes in the white matter of poor readers.

Neuroimaging studies using diffusion tensor imaging (DTI) have revealed regions of cerebral white matter with decreased microstructural organization (lowerfractional anisotropy or FA) among poor readers. We examined whether 100 hr of intensive remedial instruction affected the white matter of 8- to 10-year-old poor readers. Prior to instruction, poor readers had significantly lower FA than good readers in a region of the left anterior centrum semiovale. The instruction resulted in a change in white matter (significantly increased FA), and in the very same region. The FA increase was correlated with a decrease in radial diffusivity (but not with a change in axial diffusivity), suggesting that myelination had increased. Furthermore, the FA increase was correlated with improvement in phonological decoding ability, clarifying the cognitive locus of the effect. The results demonstrate the capability of a behavioral intervention to bring about a positive change in cortico-cortical white matter tracts.

Modeling fMRI data generated by overlapping cognitive processes with unknown onsets using Hidden Process Models.

We present a new method for modeling fMRI time series data called Hidden Process Models (HPMs). Like several earlier models for fMRI analysis, Hidden Process Models assume that the observed data is generated by a sequence of underlying mental processes that may be triggered by stimuli. HPMs go beyond these earlier models by allowing for processes whose timing may be unknown, and that might not be directly tied to specific stimuli. HPMs provide a principled, probabilistic framework for simultaneously learning the contribution of each process to the observed data, as well as the timing and identities of each instantiated process. They also provide a framework for evaluating and selecting among competing models that assume different numbers and types of underlying mental processes. We describe the HPM framework and its learning and inference algorithms, and present experimental results demonstrating its use on simulated and real fMRI data. Our experiments compare several models of the data using cross-validated data log-likelihood in an fMRI study involving overlapping mental processes whose timings are not fully known.