Using diffusion MRI data acquired with ultra-high gradient strength to improve tractography in routine-quality data.

The development of scanners with ultra-high gradient strength, spearheaded by the Human Connectome Project, has led to dramatic improvements in the spatial, angular, and diffusion resolution that is feasible for in vivo diffusion MRI acquisitions. The improved quality of the data can be exploited to achieve higher accuracy in the inference of both microstructural and macrostructural anatomy. However, such high-quality data can only be acquired on a handful of Connectom MRI scanners worldwide, while remaining prohibitive in clinical settings because of the constraints imposed by hardware and scanning time. In this study, we first update the classical protocols for tractography-based, manual annotation of major white-matter pathways, to adapt them to the much greater volume and variability of the streamlines that can be produced from today's state-of-the-art diffusion MRI data. We then use these protocols to annotate 42 major pathways manually in data from a Connectom scanner. Finally, we show that, when we use these manually annotated pathways as training data for global probabilistic tractography with anatomical neighborhood priors, we can perform highly accurate, automated reconstruction of the same pathways in much lower-quality, more widely available diffusion MRI data. The outcomes of this work include both a new, comprehensive atlas of WM pathways from Connectom data, and an updated version of our tractography toolbox, TRActs Constrained by UnderLying Anatomy (TRACULA), which is trained on data from this atlas. Both the atlas and TRACULA are distributed publicly as part of FreeSurfer. We present the first comprehensive comparison of TRACULA to the more conventional, multi-region-of-interest approach to automated tractography, and the first demonstration of training TRACULA on high-quality, Connectom data to benefit studies that use more modest acquisition protocols.

Brain connectomics predict response to treatment in social anxiety disorder.

We asked whether brain connectomics can predict response to treatment for a neuropsychiatric disorder better than conventional clinical measures. Pre-treatment resting-state brain functional connectivity and diffusion-weighted structural connectivity were measured in 38 patients with social anxiety disorder (SAD) to predict subsequent treatment response to cognitive behavioral therapy (CBT). We used a priori bilateral anatomical amygdala seed-driven resting connectivity and probabilistic tractography of the right inferior longitudinal fasciculus together with a data-driven multivoxel pattern analysis of whole-brain resting-state connectivity before treatment to predict improvement in social anxiety after CBT. Each connectomic measure improved the prediction of individuals' treatment outcomes significantly better than a clinical measure of initial severity, and combining the multimodal connectomics yielded a fivefold improvement in predicting treatment response. Generalization of the findings was supported by leave-one-out cross-validation. After dividing patients into better or worse responders, logistic regression of connectomic predictors and initial severity combined with leave-one-out cross-validation yielded a categorical prediction of clinical improvement with 81% accuracy, 84% sensitivity and 78% specificity. Connectomics of the human brain, measured by widely available imaging methods, may provide brain-based biomarkers (neuromarkers) supporting precision medicine that better guide patients with neuropsychiatric diseases to optimal available treatments, and thus translate basic neuroimaging into medical practice.

Categorical perception and influence of attention on neural consistency in response to speech sounds in adults with dyslexia.

Developmental dyslexia is a common neurodevelopmental disorder that is associated with alterations in the behavioral and neural processing of speech sounds, but the scope and nature of that association is uncertain. It has been proposed that more variable auditory processing could underlie some of the core deficits in this disorder. In the current study, magnetoencephalography (MEG) data were acquired from adults with and without dyslexia while they passively listened to or actively categorized tokens from a /ba/-/da/ consonant continuum. We observed no significant group difference in active categorical perception of this continuum in either of our two behavioral assessments. During passive listening, adults with dyslexia exhibited neural responses that were as consistent as those of typically reading adults in six cortical regions associated with auditory perception, language, and reading. However, they exhibited significantly less consistency in the left supramarginal gyrus, where greater inconsistency correlated significantly with worse decoding skills in the group with dyslexia. The group difference in the left supramarginal gyrus was evident only when neural data were binned with a high temporal resolution and was only significant during the passive condition. Interestingly, consistency significantly improved in both groups during active categorization versus passive listening. These findings suggest that adults with dyslexia exhibit typical levels of neural consistency in response to speech sounds with the exception of the left supramarginal gyrus and that this consistency increases during active versus passive perception of speech sounds similarly in the two groups.

An fMRI study of violations of social expectations: when people are not who we expect them to be.

The current study examines the effect of violations of social expectancies on the neural substrates of person perception. In an event-related fMRI experiment, participants were presented with the photographs of either Republican or Democrat politicians paired with either typical Republican or Democrat political views (e.g., "wants a smaller government" or "wants liberal supreme court judges"). Subjects were asked to form an impression of the targets using information about both their political affiliation and their political views. Of interest was the contrast between stereotypically congruent trials and stereotypically incongruent trials. The results reveal that brain regions previously involved in mentalizing (i.e., temporoparietal junction and medial prefrontal cortex) are preferentially recruited when viewing incongruent social targets.

Brain function and clinical characterization in the Boston adolescent neuroimaging of depression and anxiety study.

We present a Human Connectome Project study tailored toward adolescent anxiety and depression. This study is one of the first studies of the Connectomes Related to Human Diseases initiative and is collecting structural, functional, and diffusion-weighted brain imaging data from up to 225 adolescents (ages 14-17 years), 150 of whom are expected to have a current diagnosis of an anxiety and/or depressive disorder. Comprehensive clinical and neuropsychological evaluations and longitudinal clinical data are also being collected. This article provides an overview of task functional magnetic resonance imaging (fMRI) protocols and preliminary findings (N = 140), as well as clinical and neuropsychological characterization of adolescents. Data collection is ongoing for an additional 85 adolescents, most of whom are expected to have a diagnosis of an anxiety and/or depressive disorder. Data from the first 140 adolescents are projected for public release through the National Institutes of Health Data Archive (NDA) with the timing of this manuscript. All other data will be made publicly-available through the NDA at regularly scheduled intervals. This article is intended to serve as an introduction to this project as well as a reference for those seeking to clinical, neurocognitive, and task fMRI data from this public resource.

Age-associated reduction of asymmetry in prefrontal function and preservation of conceptual repetition priming.

Older adults often show bilateral brain activation, compared to unilateral activation in younger adults, when performing tasks in domains of age-associated cognitive impairment, such as episodic and working memory. Less is known about activation associated with performance in cognitive domains that are typically unaffected by healthy aging. We used event-related functional magnetic resonance imaging to examine age-related patterns in brain activation associated with a form of implicit memory, repetition priming, which is typically preserved in healthy aging. Sixteen younger adults and 15 nondemented older adults performed semantic judgments (abstract/concrete) on single words in a study phase. In a test phase, identical judgments were made for repeated and new words. Younger and older adults showed similar response-time benefits (repetition priming) from repeated semantic classification. Repetition priming was associated with repetition-related reductions of prefrontal activation in both groups, but the patterns of activation differed between groups. Both groups showed similar activation reductions in dorsal left inferior prefrontal cortex (LIPFC), but older adults showed less reduction than younger adults in ventral and anterior LIPFC. Activation reductions were exclusively left-lateralized for younger adults, whereas older adults showed additional reductions in multiple regions of right frontal cortices. Right prefrontal activation reductions in older adults correlated with better repetition priming and better performance on independent tests of semantic processing. Thus, reduced asymmetry of prefrontal activation reductions in healthy aging was related to conceptual repetition priming, a form of learning that is spared in aging, and with the sparing of semantic memory.

Dissociated neural representations of intensity and valence in human olfaction.

Affective experience has been described in terms of two primary dimensions: intensity and valence. In the human brain, it is intrinsically difficult to dissociate the neural coding of these affective dimensions for visual and auditory stimuli, but such dissociation is more readily achieved in olfaction, where intensity and valence can be manipulated independently. Using event-related functional magnetic resonance imaging (fMRI), we found amygdala activation to be associated with intensity, and not valence, of odors. Activity in regions of orbitofrontal cortex, in contrast, were associated with valence independent of intensity. These findings show that distinct olfactory regions subserve the analysis of the degree and quality of olfactory stimulation, suggesting that the affective representations of intensity and valence draw upon dissociable neural substrates.

Increased variability of stimulus-driven cortical responses is associated with genetic variability in children with and without dyslexia.

Individuals with dyslexia exhibit increased brainstem variability in response to sound. It is unknown as to whether increased variability extends to neocortical regions associated with audition and reading, extends to visual stimuli, and whether increased variability characterizes all children with dyslexia or, instead, a specific subset of children. We evaluated the consistency of stimulus-evoked neural responses in children with (N = 20) or without dyslexia (N = 12) as measured by magnetoencephalography (MEG). Approximately half of the children with dyslexia had significantly higher levels of variability in cortical responses to both auditory and visual stimuli in multiple nodes of the reading network. There was a significant and positive relationship between the number of risk alleles at rs6935076 in the dyslexia-susceptibility gene KIAA0319 and the degree of neural variability in primary auditory cortex across all participants. This gene has been linked with neural variability in rodents and in typical readers. These findings indicate that unstable representations of auditory and visual stimuli in auditory and other reading-related neocortical regions are present in a subset of children with dyslexia and support the link between the gene KIAA0319 and the auditory neural variability across children with or without dyslexia.

Neural correlates of rapid auditory processing are disrupted in children with developmental dyslexia and ameliorated with training: an fMRI study.

PURPOSE: Developmental dyslexia, characterized by unexpected difficulty in reading, may involve a fundamental deficit in processing rapid acoustic stimuli. Using functional magnetic resonance imaging (fMRI) we previously reported that adults with developmental dyslexia have a disruption in neural response to rapid acoustic stimuli in left prefrontal cortex. Here we examined the neural correlates of rapid auditory processing in children. METHODS: Whole-brain fMRI was performed on twenty-two children with developmental dyslexia and twenty-three typical-reading children while they listened to nonlinguistic acoustic stimuli, with either rapid or slow transitions, designed to mimic the spectro-temporal structure of consonant-vowel-consonant speech syllables. RESULTS: Typical-reading children showed activation for rapid compared to slow transitions in left prefrontal cortex. Children with developmental dyslexia did not show any differential response in these regions to rapid versus slow transitions. After eight weeks of remediation focused primarily on rapid auditory processing, phonological and linguistic training the children with developmental dyslexia showed significant improvements in language and reading skills, and exhibited activation for rapid relative to slow transitions in left prefrontal cortex. CONCLUSION: The presence of a disruption in the neural response to rapid stimuli in children with developmental dyslexia prior to remediation, coupled with significant improvement in language and reading scores and increased brain activation after remediation, gives further support to the importance of rapid auditory processing in reading development and disorders.

Neural correlates of rapid spectrotemporal processing in musicians and nonmusicians.

Our results suggest that musical training alters the functional anatomy of rapid spectrotemporal processing, resulting in improved behavioral performance along with a more efficient functional network primarily involving traditional language regions. This finding may have important implications for improving language/reading skills, especially in children struggling with dyslexia.

The neural substrates of person perception: spontaneous use of financial and moral status knowledge.

The current study examines the effect of status information on the neural substrates of person perception. In an event-related fMRI experiment, participants were presented with photographs of faces preceded with information denoting either: low or high financial status (e.g., "earns $25,000" or "earns $350,000"), or low or high moral status (e.g., "is a tobacco executive" or "does cancer research"). Participants were asked to form an impression of the targets, but were not instructed to explicitly evaluate their social status. Building on previous brain-imaging investigations, regions of interest analyses were performed for brain regions expected to support either cognitive (i.e., intraparietal sulcus) or emotional (i.e., ventromedial prefrontal cortex) components of social status perception. Activation of the intraparietal sulcus was found to be sensitive to the financial status of individuals while activation of the ventromedial prefrontal cortex was sensitive to the moral status of individuals. The implications of these results towards uncovering the neural substrates of status perception and, more broadly, the extended network of brain regions involved in person perception are discussed.

Prediction of Successful Memory Encoding from fMRI Data.

In this work, we explore the use of classification algorithms in predicting mental states from functional neuroimaging data. We train a linear support vector machine classifier to characterize spatial fMRI activation patterns. We employ a general linear model based feature extraction method and use the t-test for feature selection. We evaluate our method on a memory encoding task, using participants' subjective prediction about learning as a benchmark for our classifier. We show that the classifier achieves better than random predictions and the average accuracy is close to subject's own prediction performance. In addition, we validate our tool on a simple motor task where we demonstrate an average prediction accuracy of over 90%. Our experiments demonstrate that the classifier performance depends significantly on the complexity of the experimental design and the mental process of interest.

Dissociable contributions of prefrontal and parietal cortices to response selection.

The ability to select between possible responses to a given situation is central to human cognition. The goal of this study was to distinguish between brain areas representing candidate responses and areas selecting between competing response alternatives. Event-related fMRI data were acquired while 10 healthy adults performed a task used to examine response competition: the Eriksen flanker task. Left parietal cortex was activated by either of two manipulations that increased the need to maintain a representation of possible responses. In contrast, lateral prefrontal and rostral anterior cingulate cortices were specifically engaged by the need to select among competing response alternatives. These findings support the idea that parietal cortex is involved in activating possible responses on the basis of learned stimulus-response associations, and that prefrontal cortex is recruited when there is a need to select between competing responses.

Altered cortical visual processing in PD with hallucinations: an fMRI study.

OBJECTIVE: To compare fMRI activation during two visual stimulation paradigms in Parkinson disease (PD) subjects with chronic visual hallucinations vs PD patients who had never hallucinated. METHODS: Twelve pairs of PD subjects, matched for age, PD duration, and dopaminergic drug exposure duration, participated in this study. The authors examined group differences in activation during stroboscopic (flashing) vs no visual stimulation and kinematic (apparent motion) vs stationary visual stimulation. RESULTS: During stroboscopic stimulation, non-hallucinating PD subjects showed significantly greater activation in the parietal lobe and cingulate gyrus compared to hallucinating PD subjects. In contrast, the hallucinating subjects showed significantly greater activation in the inferior frontal gyrus and the caudate nucleus. During kinematic stimulation, non-hallucinating PD subjects showed significantly greater activation in area V5/MT, parietal lobe, and cingulate gyrus compared to hallucinating PD subjects. Hallucinating PD subjects showed significantly greater activation in the superior frontal gyrus. CONCLUSIONS: PD patients with chronic visual hallucinations respond to visual stimuli with greater frontal and subcortical activation and less visual cortical activation than non-hallucinating PD subjects. Shifting visual circuitry from posterior to anterior regions associated primarily with attention processes suggests altered network organization may play a role in the pathophysiology of visual hallucinations in PD.