Detailed connectivities have been studied in animals through invasive tracer techniques, but these invasive studies cannot be done in humans, and animal results cannot always be extrapolated to human systems. We have developed noninvasive neuronal fiber tracking for use in living humans, utilizing the unique ability of MRI to characterize water diffusion. We reconstructed fiber trajectories throughout the brain by tracking the direction of fastest diffusion (the fiber direction) from a grid of seed points, and then selected tracks that join anatomically or functionally (functional MRI) defined regions. We demonstrate diffusion tracking of fiber bundles in a variety of white matter classes with examples in the corpus callosum, geniculo-calcarine, and subcortical association pathways. Tracks covered long distances, navigated through divergences and tight curves, and manifested topological separations in the geniculo-calcarine tract consistent with tracer studies in animals and retinotopy studies in humans. Additionally, previously undescribed topologies were revealed in the other pathways. This approach enhances the power of modern imaging by enabling study of fiber connections among anatomically and functionally defined brain regions in individual human subjects.

Summary Human functional MRI (fMRI) research primarily focuses on analyzing data averaged across groups, which limits the detail, specificity, and clinical utility of fMRI resting-state functional connectivity (RSFC) and task activation maps. To push our understanding of functional brain organization to the level of individual humans, we assembled a novel MRI dataset containing five hours of RSFC data, six hours of task fMRI, multiple structural MRIs, and neuropsychological tests from each of ten adults. Using these data, we generated ten high fidelity, individual-specific functional connectomes. This individual connectome approach revealed several new types of spatial and organizational variability in brain networks, including unique network features and topologies that corresponded with structural and task-derived brain features. We are releasing this highly-sampled, individual-focused dataset as a resource for neuroscientists, and we propose precision individual connectomics as a model for future work examining the organization of healthy and diseased individual human brains.

Application of resting state functional connectivity magnetic resonance imaging (fcMRI) to the study of prematurely born infants enables assessment of the earliest forms of cerebral connectivity and characterization of its early development in the human brain. We obtained 90 longitudinal fcMRI data sets from a cohort of preterm infants aged from 26 weeks postmenstrual age (PMA) through term equivalent age at PMA-specific time points. Utilizing seed-based correlation analysis, we identified resting state networks involving varied cortical regions, the thalamus, and cerebellum. Identified networks demonstrated a regionally variable age-specific pattern of development, with more mature forms consisting of localized interhemispheric connections between homotopic counterparts. Anatomical distance was found to play a critical role in the rate of connection development. Prominent differences were noted between networks identified in term control versus premature infants at term equivalent, including in the thalamocortical connections critical for neurodevelopment. Putative precursors of the default mode network were detected in term control infants but were not identified in preterm infants, including those at term equivalent. Identified patterns of network maturation reflect the intricate relationship of structural and functional processes present throughout this important developmental period and are consistent with prior investigations of neurodevelopment in this population.

Resting state fMRI measures spontaneous, low frequency fluctuations in the BOLD signal to investigate the functional architecture of the brain. Application of this technique has allowed for the identification of various RSNs, or spatially distinct areas of the brain that demonstrate synchronous BOLD fluctuations at rest. Various methods exist for analyzing resting state data, including seed based approaches, independent component analysis, graph methods, clustering algorithms, neural networks, and pattern classifiers. Clinical applications of resting state fMRI are at an early stage of development. However, its use in presurgical planning for brain tumor and epilepsy patients demonstrates early promise, and the technique may also have a future role in providing diagnostic and prognostic information for neurological and psychiatric diseases.

BACKGROUND Blast-related traumatic brain injuries have been common in the Iraq and Afghanistan wars, but fundamental questions about the nature of these injuries remain unanswered. METHODS We tested the hypothesis that blast-related traumatic brain injury causes traumatic axonal injury, using diffusion tensor imaging (DTI), an advanced form of magnetic resonance imaging that is sensitive to axonal injury. The subjects were 63 U.S. military personnel who had a clinical diagnosis of mild, uncomplicated traumatic brain injury. They were evacuated from the field to the Landstuhl Regional Medical Center in Landstuhl, Germany, where they underwent DTI scanning within 90 days after the injury. All the subjects had primary blast exposure plus another, blast-related mechanism of injury (e.g., being struck by a blunt object or injured in a fall or motor vehicle crash). Controls consisted of 21 military personnel who had blast exposure and other injuries but no clinical diagnosis of traumatic brain injury. RESULTS Abnormalities revealed on DTI were consistent with traumatic axonal injury in many of the subjects with traumatic brain injury. None had detectible intracranial injury on computed tomography. As compared with DTI scans in controls, the scans in the subjects with traumatic brain injury showed marked abnormalities in the middle cerebellar peduncles (P<0.001), in cingulum bundles (P = 0.002), and in the right orbitofrontal white matter (P = 0.007). In 18 of the 63 subjects with traumatic brain injury, a significantly greater number of abnormalities were found on DTI than would be expected by chance (P<0.001). Follow-up DTI scans in 47 subjects with traumatic brain injury 6 to 12 months after enrollment showed persistent abnormalities that were consistent with evolving injuries. CONCLUSIONS DTI findings in U.S. military personnel support the hypothesis that blast-related mild traumatic brain injury can involve axonal injury. However, the contribution of primary blast exposure as compared with that of other types of injury could not be determined directly, since none of the subjects with traumatic brain injury had isolated primary blast injury. Furthermore, many of these subjects did not have abnormalities on DTI. Thus, traumatic brain injury remains a clinical diagnosis. (Funded by the Congressionally Directed Medical Research Program and the National Institutes of Health; ClinicalTrials.gov number, NCT00785304.)

White matter microstructural integrity was assessed using diffusion tensor imaging (DTI) in 25 young adults, 25 nondemented older adults, and 25 age-matched older adults with dementia of the Alzheimer type (DAT). For each individual, measures of anisotropy and diffusivity were obtained from atlas-transformed images in the anterior and posterior callosum and in the frontal, parietal, temporal and occipital white matter. These data revealed age differences in anisotropy and diffusivity in all assessed regions. Age effects were greater in the anterior as opposed to the posterior corpus callosum and greater in the frontal white matter than in the temporal, parietal and occipital white matter, suggesting age-associated differences in white matter that exhibit a roughly anterior-to-posterior gradient. In contrast, individuals with early-stage dementia exhibited minimal, if any, additional change in anterior regions but did show greater deterioration of white matter in posterior lobar regions. Taken collectively, these results indicate that nondemented aging is characterized by significant changes in white matter most prominently in anterior brain regions. The dissociation between the regional effects of age and dementia status suggests that the mechanisms underlying age-associated cognitive decline are likely distinct from those underlying DAT.

The brain is active even in the absence of explicit stimuli or overt responses. This activity is highly correlated within specific networks of the cerebral cortex when assessed with resting-state functional magnetic resonance imaging (fMRI) blood oxygen level-dependent (BOLD) imaging. The role of the thalamus in this intrinsic activity is unknown despite its critical role in the function of the cerebral cortex. Here we mapped correlations in resting-state activity between the human thalamus and the cerebral cortex in adult humans using fMRI BOLD imaging. Based on this functional measure of intrinsic brain activity we partitioned the thalamus into nuclear groups that correspond well with postmortem human histology and connectional anatomy inferred from nonhuman primates. This structure/function correspondence in resting-state activity was strongest between each cerebral hemisphere and its ipsilateral thalamus. However, each hemisphere was also strongly correlated with the contralateral thalamus, a pattern that is not attributable to known thalamocortical monosynaptic connections. These results extend our understanding of the intrinsic network organization of the human brain to the thalamus and highlight the potential of resting-state fMRI BOLD imaging to elucidate thalamocortical relationships.

Relating structural connectivity with functional activity is fundamentally important to understanding the brain's physiology. The thalamocortical system serves as a good model system for exploring structure/function relationships because of its well-documented anatomical connectivity. Here we performed functional and structural magnetic resonance mapping of the human thalamocortical system using intrinsic brain activity and diffusion-weighted imaging. The accuracy of these imaging techniques is tested by comparison with human histology registered to common anatomical space and connectional anatomy derived from nonhuman primates. In general, there is good overall concordance among structural, functional, and histological results which suggests that a simple model of direct anatomical connectivity between the cerebral cortex and the thalamus is capable of explaining much of the observed correlations in neuronal activity. However, important differences between structural and functional mapping results are also manifest which suggests a more complex interpretation and emphasizes the unique contributions from structural and functional mapping.