Auditory and tactile frequency representations are co-embedded in modality-defined cortical sensory systems.

Sensory information is represented and elaborated in hierarchical cortical systems that are thought to be dedicated to individual sensory modalities. This traditional view of sensory cortex organization has been challenged by recent evidence of multimodal responses in primary and association sensory areas. Although it is indisputable that sensory areas respond to multiple modalities, it remains unclear whether these multimodal responses reflect selective information processing for particular stimulus features. Here, we used fMRI adaptation to identify brain regions that are sensitive to the temporal frequency information contained in auditory, tactile, and audiotactile stimulus sequences. A number of brain regions distributed over the parietal and temporal lobes exhibited frequency-selective temporal response modulation for both auditory and tactile stimulus events, as indexed by repetition suppression effects. A smaller set of regions responded to crossmodal adaptation sequences in a frequency-dependent manner. Despite an extensive overlap of multimodal frequency-selective responses across the parietal and temporal lobes, representational similarity analysis revealed a cortical "regional landscape" that clearly reflected distinct somatosensory and auditory processing systems that converged on modality-invariant areas. These structured relationships between brain regions were also evident in spontaneous signal fluctuation patterns measured at rest. Our results reveal that multimodal processing in human cortex can be feature-specific and that multimodal frequency representations are embedded in the intrinsically hierarchical organization of cortical sensory systems.

Resting-state functional connectivity predicts longitudinal change in autistic traits and adaptive functioning in autism.

Although typically identified in early childhood, the social communication symptoms and adaptive behavior deficits that are characteristic of autism spectrum disorder (ASD) persist throughout the lifespan. Despite this persistence, even individuals without cooccurring intellectual disability show substantial heterogeneity in outcomes. Previous studies have found various behavioral assessments [such as intelligence quotient (IQ), early language ability, and baseline autistic traits and adaptive behavior scores] to be predictive of outcome, but most of the variance in functioning remains unexplained by such factors. In this study, we investigated to what extent functional brain connectivity measures obtained from resting-state functional connectivity MRI (rs-fcMRI) could predict the variance left unexplained by age and behavior (follow-up latency and baseline autistic traits and adaptive behavior scores) in two measures of outcome--adaptive behaviors and autistic traits at least 1 y postscan (mean follow-up latency = 2 y, 10 mo). We found that connectivity involving the so-called salience network (SN), default-mode network (DMN), and frontoparietal task control network (FPTCN) was highly predictive of future autistic traits and the change in autistic traits and adaptive behavior over the same time period. Furthermore, functional connectivity involving the SN, which is predominantly composed of the anterior insula and the dorsal anterior cingulate, predicted reliable improvement in adaptive behaviors with 100% sensitivity and 70.59% precision. From rs-fcMRI data, our study successfully predicted heterogeneity in outcomes for individuals with ASD that was unaccounted for by simple behavioral metrics and provides unique evidence for networks underlying long-term symptom abatement.

Functional connectivity classification of autism identifies highly predictive brain features but falls short of biomarker standards.

OBJECTIVES: Autism spectrum disorders (ASD) are diagnosed based on early-manifesting clinical symptoms, including markedly impaired social communication. We assessed the viability of resting-state functional MRI (rs-fMRI) connectivity measures as diagnostic biomarkers for ASD and investigated which connectivity features are predictive of a diagnosis. METHODS: Rs-fMRI scans from 59 high functioning males with ASD and 59 age- and IQ-matched typically developing (TD) males were used to build a series of machine learning classifiers. Classification features were obtained using 3 sets of brain regions. Another set of classifiers was built from participants' scores on behavioral metrics. An additional age and IQ-matched cohort of 178 individuals (89 ASD; 89 TD) from the Autism Brain Imaging Data Exchange (ABIDE) open-access dataset (http://fcon_1000.projects.nitrc.org/indi/abide/) were included for replication. RESULTS: High classification accuracy was achieved through several rs-fMRI methods (peak accuracy 76.67%). However, classification via behavioral measures consistently surpassed rs-fMRI classifiers (peak accuracy 95.19%). The class probability estimates, P(ASD|fMRI data), from brain-based classifiers significantly correlated with scores on a measure of social functioning, the Social Responsiveness Scale (SRS), as did the most informative features from 2 of the 3 sets of brain-based features. The most informative connections predominantly originated from regions strongly associated with social functioning. CONCLUSIONS: While individuals can be classified as having ASD with statistically significant accuracy from their rs-fMRI scans alone, this method falls short of biomarker standards. Classification methods provided further evidence that ASD functional connectivity is characterized by dysfunction of large-scale functional networks, particularly those involved in social information processing.

Individual differences in intrinsic brain connectivity predict decision strategy.

When humans are provided with ample time to make a decision, individual differences in strategy emerge. Using an adaptation of a well-studied decision making paradigm, motion direction discrimination, we probed the neural basis of individual differences in strategy. We tested whether strategies emerged from moment-to-moment reconfiguration of functional brain networks involved in decision making with task-evoked functional MRI (fMRI) and whether intrinsic properties of functional brain networks, measured at rest with functional connectivity MRI (fcMRI), were associated with strategy use. We found that human participants reliably selected one of two strategies across 2 days of task performance, either continuously accumulating evidence or waiting for task difficulty to decrease. Individual differences in decision strategy were predicted both by the degree of task-evoked activation of decision-related brain regions and by the strength of pretask correlated spontaneous brain activity. These results suggest that spontaneous brain activity constrains strategy selection on perceptual decisions.

Developmental differences in masked form priming are not driven by vocabulary growth.

As children develop into skilled readers, they are able to more quickly and accurately distinguish between words with similar visual forms (i.e., they develop precise lexical representations). The masked form priming lexical decision task is used to test the precision of lexical representations. In this paradigm, a prime (which differs by one letter from the target) is briefly flashed before the target is presented. Participants make a lexical decision to the target. Primes can facilitate reaction time by partially activating the lexical entry for the target. If a prime is unable to facilitate reaction time, it is assumed that participants have a precise orthographic representation of the target and thus the prime is not a close enough match to activate its lexical entry. Previous developmental work has shown that children and adults' lexical decision times are facilitated by form primes preceding words from small neighborhoods (i.e., very few words can be formed by changing one letter in the original word; low N words), but only children are facilitated by form primes preceding words from large neighborhoods (high N words). It has been hypothesized that written vocabulary growth drives the increase in the precision of the orthographic representations; children may not know all of the neighbors of the high N words, making the words effectively low N for them. We tested this hypothesis by (1) equating the effective orthographic neighborhood size of the targets for children and adults and (2) testing whether age or vocabulary size was a better predictor of the extent of form priming. We found priming differences even when controlling for effective neighborhood size. Furthermore, age was a better predictor of form priming effects than was vocabulary size. Our findings provide no support for the hypothesis that growth in written vocabulary size gives rise to more precise lexical representations. We propose that the development of spelling ability may be a more important factor.

Functional neuroimaging study in identical twin pairs discordant for regular cigarette smoking.

Despite the tremendous public health and financial burden of cigarette smoking, relatively little is understood about brain mechanisms that subserve smoking behavior. This study investigated the effect of lifetime regular smoking on brain processing in a reward guessing task using functional magnetic resonance imaging and a co-twin control study design in monozygotic (MZ) twin pairs that maximally controls for genetic and family background factors. Young adult (24-34 years) MZ female twin pairs (n = 15 pairs), discordant for regular smoking defined using Centers for Disease Control criteria as having smoked ≥100 cigarettes in their lifetime, were recruited from an ongoing genetic epidemiological longitudinal study of substance use and psychopathology. We applied hypothesis-driven region of interest (ROI) and whole-brain analyses to investigate the effect of regular smoking on reward processing. Reduced response to reward and punishment in regular compared with never-regular smokers was seen in hypothesis-driven ROI analysis of bilateral ventral striatum. Whole-brain analysis identified bilateral reward-processing regions that showed activation differences in response to winning or losing money but no effect of regular smoking; and frontal/parietal regions, predominantly in the right hemisphere, that showed robust effect of regular smoking but no effect of winning or losing money. Altogether, using a study design that maximally controls for group differences, we found that regular smoking had modest effects on striatal reward processing regions but robust effects on cognitive control/attentional systems.

Parcellation in left lateral parietal cortex is similar in adults and children.

A key question in developmental neuroscience involves understanding how and when the cerebral cortex is partitioned into distinct functional areas. The present study used functional connectivity MRI mapping and graph theory to identify putative cortical areas and generate a parcellation scheme of left lateral parietal cortex (LLPC) in 7 to 10-year-old children and adults. Results indicated that a majority of putative LLPC areas could be matched across groups (mean distance between matched areas across age: 3.15 mm). Furthermore, the boundaries of children's putative LLPC areas respected the boundaries generated from the adults' parcellation scheme for a majority of children's areas (13/15). Consistent with prior research, matched LLPC areas showed age-related differences in functional connectivity strength with other brain regions. These results suggest that LLPC cortical parcellation and functional connectivity mature along different developmental trajectories, with adult-like boundaries between LLPC areas established in school-age children prior to adult-like functional connectivity.

Functional network organization of the human brain.

Real-world complex systems may be mathematically modeled as graphs, revealing properties of the system. Here we study graphs of functional brain organization in healthy adults using resting state functional connectivity MRI. We propose two novel brain-wide graphs, one of 264 putative functional areas, the other a modification of voxelwise networks that eliminates potentially artificial short-distance relationships. These graphs contain many subgraphs in good agreement with known functional brain systems. Other subgraphs lack established functional identities; we suggest possible functional characteristics for these subgraphs. Further, graph measures of the areal network indicate that the default mode subgraph shares network properties with sensory and motor subgraphs: it is internally integrated but isolated from other subgraphs, much like a "processing" system. The modified voxelwise graph also reveals spatial motifs in the patterning of systems across the cortex.

Prediction of individual brain maturity using fMRI.

Group functional connectivity magnetic resonance imaging (fcMRI) studies have documented reliable changes in human functional brain maturity over development. Here we show that support vector machine-based multivariate pattern analysis extracts sufficient information from fcMRI data to make accurate predictions about individuals' brain maturity across development. The use of only 5 minutes of resting-state fcMRI data from 238 scans of typically developing volunteers (ages 7 to 30 years) allowed prediction of individual brain maturity as a functional connectivity maturation index. The resultant functional maturation curve accounted for 55% of the sample variance and followed a nonlinear asymptotic growth curve shape. The greatest relative contribution to predicting individual brain maturity was made by the weakening of short-range functional connections between the adult brain's major functional networks.

Two forms of implicit learning in childhood ADHD.

Attention deficit hyperactivity disorder (ADHD) is characterized by inattention, impulsivity, and hyperactivity mediated by frontal-striatal-cerebellar dysfunction. These circuits support implicit learning of perceptual-motor sequences but not visual-spatial context. ADHD and control children performed the Alternating Serial Reaction Time (ASRT) task, a measure of sequence learning, and the Contextual Cueing (CC) task, a measure of spatial contextual learning. Relative to controls, children with ADHD showed inconsistent ASRT learning but did not differ on CC learning. Thus, implicit sequence learning, a cognitive process mediated by frontal-striatal-cerebellar circuitry that is not under executive control, was atypical in ADHD.

Identifying Basal Ganglia divisions in individuals using resting-state functional connectivity MRI.

Studies in non-human primates and humans reveal that discrete regions (henceforth, "divisions") in the basal ganglia are intricately interconnected with regions in the cerebral cortex. However, divisions within basal ganglia nuclei (e.g., within the caudate) are difficult to identify using structural MRI. Resting-state functional connectivity MRI (rs-fcMRI) can be used to identify putative cerebral cortical functional areas in humans (Cohen et al., 2008). Here, we determine whether rs-fcMRI can be used to identify divisions in individual human adult basal ganglia. Putative basal ganglia divisions were generated by assigning basal ganglia voxels to groups based on the similarity of whole-brain functional connectivity correlation maps using modularity optimization, a network analysis tool. We assessed the validity of this approach by examining the spatial contiguity and location of putative divisions and whether divisions' correlation maps were consistent with previously reported patterns of anatomical and functional connectivity. Spatially constrained divisions consistent with the dorsal caudate, ventral striatum, and dorsal caudal putamen could be identified in each subject. Further, correlation maps associated with putative divisions were consistent with their presumed connectivity. These findings suggest that, as in the cerebral cortex, subcortical divisions can be identified in individuals using rs-fcMRI. Developing and validating these methods should improve the study of brain structure and function, both typical and atypical, by allowing for more precise comparison across individuals.

An abbreviated implicit spatial context learning task that yields greater learning.

The spatial contextual cuing task (SCCT) (Chun & Jiang, 1998) is an implicit learning task that appears to depend on the medial temporal lobes. This unusual combination has been of interest in functional imaging studies and research with clinical populations, where testing time is at a premium. However, the original version of the SCCT is time-consuming. In this study, 29 young adults (age range, 18-22 years) completed the SCCT, in which participants respond to the orientation of a target in arrays containing 11 distractors. Either 12 (original version) or 6 (abbreviated version) arrays repeated across the experiment, with the remaining novel arrays being generated randomly. Results revealed that the magnitude of learning (faster responses to repeated versus novel arrays) was larger when there were fewer repeated arrays, with no explicit awareness in most participants. Thus, the abbreviated version remained implicit, with the additional benefit of increasing the magnitude of learning.

The fMRI success rate of children and adolescents: typical development, epilepsy, attention deficit/hyperactivity disorder, and autism spectrum disorders.

Functional magnetic resonance imaging (fMRI) in children is increasingly used in clinical application and in developmental research; however, little is known how pediatric patient and typically developing populations successfully complete studies. We examined pediatric success rates with epilepsy, attention deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and typically developing children (TYP). We also examined the affect of age, and, for ADHD populations, medication status on success rates. We defined a successful fMRI individual run when the data were interpretable and included in group statistics. For unsuccessful runs, datasets with excessive motion or floor task performance were categorized when possible. All clinical groups scanned less successfully than controls; medication status did not affect ADHD success (epilepsy, 80%; ADHD (off methylphenidate), 77%; ADHD (on methylphenidate), 81%; ASD, 70%; TYP, 87%). Ten to 18-year-old had a significantly greater scan success rate than 4- to 6-year-old; adolescents (13- to 18-year-old) demonstrated greater scan success rates than 7- to 9-year-old. Success rate for completing an entire battery of experimental runs (n = 2-6), varied between 50-59% for patient populations and 69% for TYP (79% when excluding 4- to 6-year-old). Success rate for completing one run from a battery was greater than 90% for all groups, except for ASD (81%). These data suggest 20-30% more children should be recruited in these patient groups, but only 10-20% for TYP for research studies. Studies with 4- to 6-year-olds may require 20-40% additional participants; studies with 10- to 18-year-olds may require 10-15% additional participants.

Functional connectivity of the inferior frontal cortex changes with age in children with autism spectrum disorders: a fcMRI study of response inhibition.

Unmasking the neural basis of neurodevelopmental disorders, such as autism spectrum disorders (ASD), requires studying functional connectivity during childhood when cognitive skills develop. A functional connectivity magnetic resonance imaging (fcMRI) analysis was performed on data collected during Go/NoGo task performance from 24 children ages 8-12 years (12 with ASD; 12 controls matched on age and intellectual functioning). We investigated the connectivity of the left and right inferior frontal cortex (IFC; BA 47), key regions for response inhibition, with other active regions in frontal, striatal, and parietal cortex. Groups did not differ on behavioral measures or functional connectivity of either IFC region. A trend for reduced connectivity in the right IFC for the ASD group was revealed when controlling for age. In the ASD group, there was a significant negative correlation between age and 2 right IFC correlation pairs: right IFC-bilateral presupplementary motor area (BA 6) and right IFC-right caudate. Compared with typical controls, children with ASD may not have gross differences in IFC functional connectivity during response inhibition, which contrasts with an adult study of ASD that reported reduced functional connectivity. This discrepancy suggests an atypical developmental trajectory in ASD for right IFC connectivity with other neural regions supporting response inhibition.

Intact implicit learning of spatial context and temporal sequences in childhood autism spectrum disorder.

Autism spectrum disorder (ASD) is defined by atypicalities in domains that are posited to rely on implicit learning processes such as social communication, language, and motor behavior. The authors examined 2 forms of implicit learning in 14 children with high-functioning ASD (10 of whom were diagnosed with Asperger's syndrome) and 14 control children, learning of spatial context known to be mediated by the medial temporal lobes (using the contextual cueing task) and of sequences known to be mediated by frontal-striatal and frontal-cerebellar circuits (using the alternating serial reaction time task). Both forms of learning were unimpaired in ASD. Spatial contextual implicit learning was spared in ASD despite slower visual search of spatial displays. The present findings provide evidence for the integrity of learning processes dependent on integration of spatial and sequential contextual information in high-functioning children with ASD.

Developmental differences in cognitive control of socio-affective processing.

We examined developmental differences in cognitive control in the context of distracting communicative cues varying in socio-affective significance. Adults and children (6-13 years) performed a Stroop-type task that required manual responses to a target word (LEFT/RIGHT) in the context of to-be-ignored spatial cues that were symbolic (arrow pointing left or right), social (left/right averted eye gaze in faces), or socio-emotional (happy, angry and fearful faces with left/right averted eye gaze). On the basis of the finding that accuracy was lower in the context of spatially incongruent than congruent cues, it was concluded that spatial direction, cued by both arrows and eye gaze, interfered with response selection. Interference did not differ between adults and children indicating that cognitive control of spatial attention directed by symbolic and social information is mature by 6 years. Interference from averted eye gaze was insensitive to the valence of facial emotion in adults and in children between 6-9 but not 10-13 years. Older children showed more interference from averted eye gaze in angry faces than younger children or adults. Thus, cognitive control of socio-affective processing differs in the preadolescent years relative to earlier in late childhood and adulthood.

The effect of divided attention on global judgment of learning accuracy.

This study examined the effect of divided attention (DA) on global judgment of learning (JOL) accuracy in a multitrial list learning paradigm. A word monitoring task was used to divide attention. Participants were assigned to an attention condition (DA at encoding, DA at judgment, DA at retrieval, or focused attention) and completed 4 learning trials, each comprising a study, judgment, and recall phase. Participants showed greater overconfidence in the DA at encoding (Trial 2) and DA at retrieval (Trials 1 and 2) conditions than in the focused attention condition. DA atjudgment did not affect JOL accuracy, and there was no effect of DA in Trials 3 and 4 on JOL accuracy across all attention conditions. Results indicate that participants consider conditions of encoding and retrieval but do not engage in recall when forming global JOLs. These findings suggest that people rely on extrinsic cues when making repeated, global metamemoryjudgments.