Kevin Jarbo

High-definition fiber tractography of the human brain: neuroanatomical validation and neurosurgical applications.

BACKGROUND High-definition fiber tracking (HDFT) is a novel combination of processing, reconstruction, and tractography methods that can track white matter fibers from cortex, through complex fiber crossings, to cortical and subcortical targets with subvoxel resolution. OBJECTIVE To perform neuroanatomical validation of HDFT and to investigate its neurosurgical applications. METHODS Six neurologically healthy adults and 36 patients with brain lesions were studied. Diffusion spectrum imaging data were reconstructed with a Generalized Q-Ball Imaging approach. Fiber dissection studies were performed in 20 human brains, and selected dissection results were compared with tractography. RESULTS HDFT provides accurate replication of known neuroanatomical features such as the gyral and sulcal folding patterns, the characteristic shape of the claustrum, the segmentation of the thalamic nuclei, the decussation of the superior cerebellar peduncle, the multiple fiber crossing at the centrum semiovale, the complex angulation of the optic radiations, the terminal arborization of the arcuate tract, and the cortical segmentation of the dorsal Broca area. From a clinical perspective, we show that HDFT provides accurate structural connectivity studies in patients with intracerebral lesions, allowing qualitative and quantitative white matter damage assessment, aiding in understanding lesional patterns of white matter structural injury, and facilitating innovative neurosurgical applications. High-grade gliomas produce significant disruption of fibers, and low-grade gliomas cause fiber displacement. Cavernomas cause both displacement and disruption of fibers. CONCLUSION Our HDFT approach provides an accurate reconstruction of white matter fiber tracts with unprecedented detail in both the normal and pathological human brain. Further studies to validate the clinical findings are needed.

Converging structural and functional connectivity of orbitofrontal, dorsolateral prefrontal, and posterior parietal cortex in the human striatum.

Modification of spatial attention via reinforcement learning (Lee and Shomstein, 2013) requires the integration of reward, attention, and executive processes. Corticostriatal pathways are an ideal neural substrate for this integration because these projections exhibit a globally parallel (Alexander et al., 1986), but locally overlapping (Haber, 2003), topographical organization. Here we explore whether there are unique striatal regions that exhibit convergent anatomical connections from orbitofrontal cortex, dorsolateral prefrontal cortex, and posterior parietal cortex. Deterministic fiber tractography on diffusion spectrum imaging data from neurologically healthy adults (N = 60) was used to map frontostriatal and parietostriatal projections. In general, projections from cortex were organized according to both a medial–lateral and a rostral–caudal gradient along the striatal nuclei. Within rostral aspects of the striatum, we identified two bilateral convergence zones (one in the caudate nucleus and another in the putamen) that consisted of voxels with unique projections from orbitofrontal cortex, dorsolateral prefrontal cortex, and parietal regions. The distributed cortical connectivity of these striatal convergence zones was confirmed with follow-up functional connectivity analysis from resting state fMRI data, in which a high percentage of structurally connected voxels also showed significant functional connectivity. The specificity of this convergent architecture to these regions of the rostral striatum was validated against control analysis of connectivity within the motor putamen. These results delineate a neurologically plausible network of converging corticostriatal projections that may support the integration of reward, executive control, and spatial attention that occurs during spatial reinforcement learning.

In vivo quantification of global connectivity in the human corpus callosum

Histological studies on nonhuman primates have shown a rich topography of homotopic (i.e., going to the same regions) or heterotopic (i.e., going to different regions) callosal projections. Unfortunately, a complete within-subject mapping of commissural projections in humans has been limited due to the inability of typical imaging methods to detect lateral projections in posterior cortical regions. Here, we set out to map callosal projection connectivity, at the single subject level (N=6), by combining high angular resolution diffusion weighted imaging and a novel multi-stage, region-of-interest (ROI) based fiber tracking approach. With these methods we were able to obtain a consistent increase in coverage of lateral projections to posterior cortical regions. Using 70 automatically segmented ROIs in each hemisphere and permutation statistics, we characterized significant interhemispheric connectivity patterns within each subject and observed: (1) consistent projections to frontal, parietal and occipital, but not temporal, areas, (2) a greater relative proportion of homotopic than heterotopic connections, and (3) commissural projections to the basal ganglia and thalamus that are consistent with human and nonhuman primate neuroanatomical literature. These results illustrate the first full connectivity analysis of the human corpus callosum, revealing several patterns consistent with histological findings in the nonhuman primate.

In Vivo Mapping of Microstructural Somatotopies in the Human Corticospinal Pathways

The human corticospinal pathway is organized in a body-centric (i.e., somatotopic) manner that begins in cortical cell bodies and is maintained in the axons as they project through the midbrain on their way to spinal motor neurons. The subcortical segment of this somatotopy has been described using histological methods on non-human primates but only coarsely validated from lesion studies in human patient populations. Using high definition fiber tracking (HDFT) techniques, we set out to provide the first in vivo quantitative description of the midbrain somatotopy of corticospinal fibers in humans. Multi-shell diffusion imaging and deterministic fiber tracking were used to map white matter bundles that originate in the neocortex, navigate complex fiber crossings, and project through the midbrain. These fiber bundles were segmented into premotor (dorsal premotor, ventral premotor, and supplementary motor area) and primary motor sections based on the cortical origin of each fiber streamline. With HDFT, we were able to reveal several unique corticospinal patterns, including the cortical origins of ventral premotor fibers and small (∼ 1-2 mm) shifts in the midbrain location of premotor versus primary motor cortex fibers. More importantly, within the relatively small diameter of the pyramidal tracts (∼ 5 mm), we were able to map and quantify the direction of the corticospinal somatotopy. These results show how an HDFT approach to white matter mapping provides the first in vivo, quantitative mapping of subcortical corticospinal topographies at resolutions previously only available with postmortem histological techniques.

Microstructural organizational patterns in the human corticostriatal system

The axons that project into the striatum are known to segregate according to macroscopic cortical systems; however, the within-region organization of these fibers has yet to be described in humans. We used in vivo fiber tractography, in neurologically healthy adults, to map white matter bundles that originate in different neocortical areas, navigate complex fiber crossings, and project into the striatum. As expected, these fibers were generally segregated according to cortical origin. Within a subset of pathways, a patched pattern of inputs was observed, consistent with previous ex vivo histological studies. In projections from the prefrontal cortex, we detected a topography in which fibers from rostral prefrontal areas projected mostly to rostral parts of the striatum and vice versa for inputs originating in caudal cortical areas. Importantly, within this prefrontal system there was also an asymmetry in the subset of divergent projections, with more fibers projecting in a posterior direction than anterior. This asymmetry of information projecting into the basal ganglia was predicted by previous network-level computational models. A rostral-caudal topography was also present at the local level in otherwise somatotopically organized fibers projecting from the motor cortex. This provides clear evidence that the longitudinal organization of input fields, observed at the macroscopic level across cortical systems, is also found at the microstructural scale at which information is segregated as it enters the human basal ganglia.

High-definition fiber tracking for assessment of neurological deficit in a case of traumatic brain injury: finding, visualizing, and interpreting small sites of damage

For patients with traumatic brain injury (TBI), current clinical imaging methods generally do not provide highly detailed information about the location of axonal injury, severity of injury, or expected recovery. In a case of severe TBI, the authors applied a novel high-definition fiber tracking (HDFT) to directly visualize and quantify the degree of axonal fiber damage and predict functional deficits due to traumatic axonal injury and loss of cortical projections. This 32-year-old man sustained a severe TBI. Computed tomography and MRI revealed an area of hemorrhage in the basal ganglia with mass effect, but no specific information on the location of axonal injury could be obtained from these studies. Examinations of the patient at Week 3 and Week 8 after TBI revealed motor weaknesses of the left extremities. Four months postinjury, 257-direction diffusion spectrum imaging and HDFT analysis was performed to evaluate the degree of axonal damage in the motor pathway and quantify asymmetries in the left and right axonal pathways. High-definition fiber tracking was used to follow corticospinal and corona radiata pathways from the cortical surface to the midbrain and quantify projections from motor areas. Axonal damage was then localized by assessing the number of descending fibers at the level of the cortex, internal capsule, and midbrain. The motor deficit apparent in the clinical examinations correlated with the axonal losses visualized using HDFT. Fiber loss estimates at 4 months postinjury accurately predicted the nature of the motor deficits (severe, focal left-hand weakness) when other standard clinical imaging modalities did not. A repeat scan at 10 months postinjury, when edema and hemorrhage had receded, replicated the fiber loss. Using HDFT, the authors accurately identified the presence and location of damage to the underlying white matter in this patient with TBI. Detailed information of injury provided by this novel technique holds future potential for precise neuroimaging assessment of TBI.

Quantifying White Matter Structural Integrity With High-Definition Fiber Tracking in Traumatic Brain Injury

There is an urgent, unmet demand for definitive biological diagnosis of traumatic brain injury (TBI) to pinpoint the location and extent of damage. We have developed High-Definition Fiber Tracking, a 3 T magnetic resonance imaging-based diffusion spectrum imaging and tractography analysis protocol, to quantify axonal injury in military and civilian TBI patients. A novel analytical methodology quantified white matter integrity in patients with TBI and healthy controls. Forty-one subjects (23 TBI, 18 controls) were scanned with the High-Definition Fiber Tracking diffusion spectrum imaging protocol. After reconstruction, segmentation was used to isolate bilateral hemisphere homologues of eight major tracts. Integrity of segmented tracts was estimated by calculating homologue correlation and tract coverage. Both groups showed high correlations for all tracts. TBI patients showed reduced homologue correlation and tract spread and increased outlier count (correlations>2.32 SD below control mean). On average, 6.5% of tracts in the TBI group were outliers with substantial variability among patients. Number and summed deviation of outlying tracts correlated with initial Glasgow Coma Scale score and 6-month Glasgow Outcome Scale-Extended score. The correlation metric used here can detect heterogeneous damage affecting a low proportion of tracts, presenting a potential mechanism for advancing TBI diagnosis.

Sensory uncertainty impacts avoidance during spatial decisions

When making risky spatial decisions, humans incorporate estimates of sensorimotor variability and costs on outcomes to bias their spatial selections away from regions that incur feedback penalties. Since selection variability depends on the reliability of sensory signals, increasing the spatial variance of targets during visually guided actions should increase the degree of this avoidance. Healthy adult participants (N = 20) used a computer mouse to indicate their selection of the mean of a target, represented as a 2D Gaussian distribution of dots presented on a computer display. Reward feedback on each trial corresponded to the estimation error of the selection. Either increasing or decreasing the spatial variance of the dots modulated the spatial uncertainty of the target. A non-target distractor cue was presented as an adjacent distribution of dots. On a subset of trials, feedback scores were penalized with increased proximity to the distractor mean. As expected, increasing the spatial variance of the target distribution increased selection variability. More importantly, on trials where proximity to the distractor cue incurred a penalty, increasing variance of the target increased selection bias away from the distractor cue and prolonged reaction times. These results confirm predictions that increased sensory uncertainty increases avoidance during risky spatial decisions.

Estimation of Voxelwise Effective Connectivities: Applications to High Connectivity Sub-Regions within Hippocampal and within Corticostriatal Networks

Standard BOLD connectivity analyses depend on aggregating the signals of individual voxel within regions of interest (ROIs). In certain cases, this aggregation implies a loss of valuable functional and anatomical information about sub-regions of voxels that drive the ROI level connectivity. We describe a data-driven statistical search method that identifies the voxels that are chiefly responsible for exchanging signals between regions of interest that are known to be effectively connected. We apply the method to high-resolution resting state functional magnetic resonance imaging (rs-fMRI) data from medial temporal lobe regions of interest of a single healthy individual measured repeated times over a year and a half. The method successfully recovered densely connected voxels within larger ROIs of entorhinal cortex and hippocampus subfields consistent with the well-known medial temporal lobe structural connectivity. To assess the performance of our method in more common scanning protocols we apply it to resting state fMRI data of corticostriatal regions of interest for 50 healthy individuals. The method recovered densely connected voxels within the caudate nucleus and the putamen in good qualitative agreement with structural connectivity measurements. We describe related methods for estimation of effective connections at the voxel level that merit investigation.