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.

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.

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.

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.

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.

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.

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.

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.

fMRI investigation of working memory for faces in autism: visual coding and underconnectivity with frontal areas.

Brain activation and functional connectivity were investigated in high functioning autism using functional magnetic resonance imaging in an n-back working memory task involving photographic face stimuli. The autism group showed reliably lower activation compared with controls in the inferior left prefrontal area (involved in verbal processing and working memory maintenance) and the right posterior temporal area (associated with theory of mind processing). The participants with autism also showed activation in a somewhat different location in the fusiform area than the control participants. These results suggest that the neural circuitry of the brain for face processing in autism may be analyzing the features of the face more as objects and less in terms of their human significance. The functional connectivity results revealed that the abnormal fusiform activation was embedded in a larger context of smaller and less synchronized networks, particularly indicating lower functional connectivity with frontal areas. In contrast to the underconnectivity with frontal areas, the autism group showed no underconnectivity among posterior cortical regions. These results extend previous findings of abnormal face perception in autism by demonstrating that the abnormalities are embedded in an abnormal cortical network that manages to perform the working memory task proficiently, using a visually oriented, asocial processing style that minimizes reliance on prefrontal areas.

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.

Modifying the brain activation of poor readers during sentence comprehension with extended remedial instruction: a longitudinal study of neuroplasticity.

This study used fMRI to longitudinally assess the impact of intensive remedial instruction on cortical activation among 5th grade poor readers during a sentence comprehension task. The children were tested at three time points: prior to remediation, after 100 h of intensive instruction, and 1 year after the instruction had ended. Changes in brain activation were also measured among 5th grade good readers at the same time points for comparison. The central finding was that prior to instruction, the poor readers had significantly less activation than good readers bilaterally in the parietal cortex. Immediately after instruction, poor readers made substantial gains in reading ability, and demonstrated significantly increased activation in the left angular gyrus and the left superior parietal lobule. Activation in these regions continued to increase among poor readers 1 year post-remediation, resulting in a normalization of the activation. These results are interpreted as reflecting changes in the processes involved in word-level and sentence-level assembly. Areas of overactivation were also found among poor readers in the medial frontal cortex, possibly indicating a more effortful and attentive guided reading strategy.

A decrease in brain activation associated with driving when listening to someone speak.

Behavioral studies have shown that engaging in a secondary task, such as talking on a cellular telephone, disrupts driving performance. This study used functional magnetic resonance imaging (fMRI) to investigate the impact of concurrent auditory language comprehension on the brain activity associated with a simulated driving task. Participants steered a vehicle along a curving virtual road, either undisturbed or while listening to spoken sentences that they judged as true or false. The dual-task condition produced a significant deterioration in driving accuracy caused by the processing of the auditory sentences. At the same time, the parietal lobe activation associated with spatial processing in the undisturbed driving task decreased by 37% when participants concurrently listened to sentences. The findings show that language comprehension performed concurrently with driving draws mental resources away from the driving and produces deterioration in driving performance, even when it does not require holding or dialing a phone.

Brain activation during sentence comprehension among good and poor readers.

This study sought to increase current understanding of the neuropsychological basis of poor reading ability by using fMRI to examine brain activation during a visual sentence comprehension task among good and poor readers in the third (n = 32) and fifth (n = 35) grades. Reading ability, age, and the combination of both factors made unique contributions to cortical activation. The main finding was of parietotemporal underactivation (less activation than controls) among poor readers at the 2 grade levels. A positive linear relationship (spanning both the poor and good readers) was found between reading ability and activation in the left posterior middle temporal and postcentral gyri and in the right inferior parietal lobule such that activation increased with reading ability. Different developmental trajectories characterized good and poor readers in the left angular gyrus: activation increased with age among good readers, a change that failed to occur among poor readers. The parietotemporal cortex is discussed in terms of its role in reading acquisition, with the left angular gyrus playing a key role. It is proposed that the functioning of the cortical network underlying reading is dependent on a combination of interacting factors, including physiological maturation, neural integrity, skill level, and the nature of the task.

Neural basis of dyslexia: a comparison between dyslexic and nondyslexic children equated for reading ability.

Adults and children with developmental dyslexia exhibit reduced parietotemporal activation in functional neuroimaging studies of phonological processing. These studies used age-matched and/or intelligence quotient-matched control groups whose reading ability and scanner task performance were often superior to that of the dyslexic group. It is unknown, therefore, whether differences in activation reflect simply poorer performance in the scanner, the underlying level of reading ability, or more specific neural correlates of dyslexia. To resolve this uncertainty, we conducted a functional magnetic resonance imaging study, with a rhyme judgment task, in which we compared dyslexic children with two control groups: age-matched children and reading-matched children (younger normal readers equated for reading ability or scanner-performance to the dyslexic children). Dyslexic children exhibited reduced activation relative to both age-matched and reading-matched children in the left parietotemporal cortex and five other regions, including the right parietotemporal cortex. The dyslexic children also exhibited reduced activation bilaterally in the parietotemporal cortex when compared with children equated for task performance during scanning. Nine of the 10 dyslexic children exhibited reduced left parietotemporal activation compared with their individually selected age-matched or reading-matched control children. Additionally, normal reading fifth graders showed more activation in the same bilateral parietotemporal regions than normal-reading third graders. These findings indicate that the activation differences seen in the dyslexic children cannot be accounted for by either current reading level or scanner task performance, but instead represent a distinct developmental atypicality in the neural systems that support learning to read.

Inhibitory control in high-functioning autism: decreased activation and underconnectivity in inhibition networks.

BACKGROUND: Inhibiting prepotent responses is critical to optimal cognitive and behavioral function across many domains. Several behavioral studies have investigated response inhibition in autism, and the findings varied according to the components involved in inhibition. There has been only one published functional magnetic resonance imaging (fMRI) study so far on inhibition in autism, which found greater activation in participants with autism than control participants. METHODS: This study investigated the neural basis of response inhibition in 12 high-functioning adults with autism and 12 age- and intelligence quotient (IQ)-matched control participants during a simple response inhibition task and an inhibition task involving working memory. RESULTS: In both inhibition tasks, the participants with autism showed less brain activation than control participants in areas often found to be active in response inhibition tasks, namely the anterior cingulate cortex. In the more demanding inhibition condition, involving working memory, the participants with autism showed more activation than control participants in the premotor areas. In addition to the activation differences, the participants with autism showed lower levels of synchronization between the inhibition network (anterior cingulate gyrus, middle cingulate gyrus, and insula) and the right middle and inferior frontal and right inferior parietal regions. CONCLUSIONS: The results indicate that the inhibition circuitry in the autism group is activated atypically and is less synchronized, leaving inhibition to be accomplished by strategic control rather than automatically. At the behavioral level, there was no difference between the groups.

Prediction of children's reading skills using behavioral, functional, and structural neuroimaging measures.

The ability to decode letters into language sounds is essential for reading success, and accurate identification of children at high risk for decoding impairment is critical for reducing the frequency and severity of reading impairment. We examined the utility of behavioral (standardized tests), and functional and structural neuroimaging measures taken with children at the beginning of a school year for predicting their decoding ability at the end of that school year. Specific patterns of brain activation during phonological processing and morphology, as revealed by voxel-based morphometry (VBM) of gray and white matter densities, predicted later decoding ability. Further, a model combining behavioral and neuroimaging measures predicted decoding outcome significantly better than either behavioral or neuroimaging models alone. Results were validated using cross-validation methods. These findings suggest that neuroimaging methods may be useful in enhancing the early identification of children at risk for poor decoding and reading skills.

A developmental study of the structural integrity of white matter in autism.

Diffusion tensor imaging was used to examine developmental changes in the organization of white matter in a large sample of male participants with autism and controls between the ages of 10 and 35 years. Participants with autism had lower fractional anisotropy in areas within and near the corpus callosum and in the right retrolenticular portion of the internal capsule. Only one area, in the posterior limb of the right internal capsule, showed an interaction between age and group. The findings suggest that reductions in the structural integrity of white matter in autism persist into adulthood. These reductions may underlie the behavioral pattern observed in autism, as well as findings of reduced functional connectivity in functional magnetic resonance imaging signal between activating cortical areas.

Sentence comprehension in autism: thinking in pictures with decreased functional connectivity.

Comprehending high-imagery sentences like The number eight when rotated 90 degrees looks like a pair of eyeglasses involves the participation and integration of several cortical regions. The linguistic content must be processed to determine what is to be mentally imaged, and then the mental image must be evaluated and related to the sentence. A theory of cortical underconnectivity in autism predicts that the interregional collaboration required between linguistic and imaginal processing in this task would be underserved in autism. This functional MRI study examined brain activation in 12 participants with autism and 13 age- and IQ-matched control participants while they processed sentences with either high- or low-imagery content. The analysis of functional connectivity among cortical regions showed that the language and spatial centres in the participants with autism were not as well synchronized as in controls. In addition to the functional connectivity differences, there was also a group difference in activation. In the processing of low-imagery sentences (e.g. Addition, subtraction and multiplication are all math skills), the use of imagery is not essential to comprehension. Nevertheless, the autism group activated parietal and occipital brain regions associated with imagery for comprehending both the low and high-imagery sentences, suggesting that they were using mental imagery in both conditions. In contrast, the control group showed imagery-related activation primarily in the high-imagery condition. The findings provide further evidence of underintegration of language and imagery in autism (and hence expand the understanding of underconnectivity) but also show that people with autism are more reliant on visualization to support language comprehension.

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.