Frontal-subcortical cognitive and limbic feedback loops modulate higher cognitive functioning. The final step in these feedback loops is the thalamo-cortical projection through the anterior limb of the internal capsule (AL-IC). Using diffusion tensor imaging (DTI), we evaluated abnormalities in the AL-IC fiber tract in schizophrenia. Participants comprised 16 chronic schizophrenia patients and 19 male, normal controls, who were group matched for handedness, age, and parental socioeconomic status, and underwent DTI on a 1.5 Tesla GE system. We measured the diffusion indices, fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD), and manually segmented, based on FA maps, AL-IC volume, normalized for intracranial contents (ICC). The results showed a significant reduction in the ICC-corrected volume of the AL-IC in schizophrenia, but did not show diffusion measure group differences in the AL-IC in FA, MD, RD or AD. In addition, in the schizophrenia patients, AL-IC FA correlated positively with performance on measures of spatial and verbal declarative/episodic memory, and right AL-IC ICC-corrected volume correlated positively with more perseverative responses on the Wisconsin Card Sort Test (WCST). We found a reduction in AL-IC ICC-corrected volume in schizophrenia, without FA, MD, RD or AD group differences, implicating the presence of a structural abnormality in schizophrenia in this subcortical white matter region which contains important cognitive, and limbic feedback pathways that modulate prefrontal cortical function. Despite not demonstrating a group difference in FA, we found that AL-IC FA was a good predictor of spatial and verbal declarative/episodic memory performance in schizophrenia.
The dorsolateral prefrontal cortex (DLPFC) is a brain region that has figured prominently in studies of schizophrenia and working memory, yet the exact neuroanatomical localization of this brain region remains to be defined. DLPFC primarily involves the superior frontal gyrus and middle frontal gyrus (MFG). The latter, however is not a single neuroanatomical entity but instead is comprised of rostral (anterior, middle, and posterior) and caudal regions. In this study we used structural MRI to develop a method for parcellating MFG into its component parts. We focused on this region of DLPFC because it includes BA46, a region involved in working memory. We evaluated volume differences in MFG in 20 patients with chronic schizophrenia and 20 healthy controls. Mid-rostral MFG (MR-MFG) was delineated within the rostral MFG using anterior and posterior neuroanatomical landmarks derived from cytoarchitectonic definitions of BA46. Gray matter volumes of MR-MFG were then compared between groups, and a significant reduction in gray matter volume was observed (p<0.008), but not in other areas of MFG (i.e., anterior or posterior rostral MFG, or caudal regions of MFG). Our results demonstrate that volumetric alterations in MFG gray matter are localized exclusively to MR-MFG. 3D reconstructions of the cortical surface made it possible to follow MFG into its anterior part, where other approaches have failed. This method of parcellation offers a more precise way of measuring MR-MFG that will likely be important in further documentation of DLPFC anomalies in schizophrenia.
Registration uncertainty may be important information to convey to a surgeon when surgical decisions are taken based on registered image data. However, conventional non-rigid registration methods only provide the most likely deformation. In this paper we show how to determine the registration uncertainty, as well as the most likely deformation, by using an elastic Bayesian registration framework that generates a dense posterior distribution on deformations. We model both the likelihood and the elastic prior on deformations with Boltzmann distributions and characterize the posterior with a Markov Chain Monte Carlo algorithm. We introduce methods that summarize the high-dimensional uncertainty information and show how these summaries can be visualized in a meaningful way. Based on a clinical neurosurgical dataset, we demonstrate the importance that uncertainty information could have on neurosurgical decision making.
In this paper, we analyze Markov Random Field (MRF) as a spatial regularizer in fMRI detection. The low signal-to-noise ratio (SNR) in fMRI images presents a serious challenge for detection algorithms, making regularization necessary to achieve good detection accuracy. Gaussian smoothing, traditionally employed to boost SNR, often produces over-smoothed activation maps. Recently, the use of MRF priors has been suggested as an alternative regularization approach. However, solving for an optimal configuration of the MRF is NP-hard in general. In this work, we investigate fast inference algorithms based on the Mean Field approximation in application to MRF priors for fMRI detection. Furthermore, we propose a novel way to incorporate anatomical information into the MRF-based detection framework and into the traditional smoothing methods. Intuitively speaking, the anatomical evidence increases the likelihood of activation in the gray matter and improves spatial coherency of the resulting activation maps within each tissue type. Validation using the receiver operating characteristic (ROC) analysis and the confusion matrix analysis on simulated data illustrates substantial improvement in detection accuracy using the anatomically guided MRF spatial regularizer. We further demonstrate the potential benefits of the proposed method in real fMRI signals of reduced length. The anatomically guided MRF regularizer enables significant reduction of the scan length while maintaining the quality of the resulting activation maps.
Two key aspects of coupled multi-object shape analysis and atlas generation are the choice of representation and subsequent registration methods used to align the sample set. For example, a typical brain image can be labeled into three structures: grey matter, white matter and cerebrospinal fluid. Many manipulations such as interpolation, transformation, smoothing, or registration need to be performed on these images before they can be used in further analysis. Current techniques for such analysis tend to trade off performance between the two tasks, performing well for one task but developing problems when used for the other. This article proposes to use a representation that is both flexible and well suited for both tasks. We propose to map object labels to vertices of a regular simplex, e.g . the unit interval for two labels, a triangle for three labels, a tetrahedron for four labels, etc. This representation, which is routinely used in fuzzy classification, is ideally suited for representing and registering multiple shapes. On closer examination, this representation reveals several desirable properties: algebraic operations may be done directly, label uncertainty is expressed as a weighted mixture of labels (probabilistic interpretation), interpolation is unbiased toward any label or the background, and registration may be performed directly. We demonstrate these properties by using label space in a gradient descent based registration scheme to obtain a probabilistic atlas. While straightforward, this iterative method is very slow, could get stuck in local minima, and depends heavily on the initial conditions. To address these issues, two fast methods are proposed which serve as coarse registration schemes following which the iterative descent method can be used to refine the results. Further, we derive an analytical formulation for direct computation of the "group mean" from the parameters of pairwise registration of all the images in the sample set. We show results on richly labeled 2D and 3D data sets.
We demonstrate an automated, multi-level method to segment white matter brain lesions and apply it to lupus. The method makes use of local morphometric features based on multiple MR sequences, including T1-weighted, T2-weighted, and fluid attenuated inversion recovery. After preprocessing, including co-registration, brain extraction, bias correction, and intensity standardization, 49 features are calculated for each brain voxel based on local morphometry. At each level of segmentation a supervised classifier takes advantage of a different subset of the features to conservatively segment lesion voxels, passing on more difficult voxels to the next classifier. This multi-level approach allows for a fast lesion classification method with tunable trade-offs between sensitivity and specificity producing accuracy comparable to a human rater.
We present a fully automatic lung lobe segmentation algorithm that is effective in high resolution computed tomography (CT) datasets in the presence of confounding factors such as incomplete fissures (anatomical structures indicating lobe boundaries), advanced disease states, high body mass index (BMI), and low-dose scanning protocols. In contrast to other algorithms that leverage segmentations of auxiliary structures (esp. vessels and airways), we rely only upon image features indicating fissure locations. We employ a particle system that samples the image domain and provides a set of candidate fissure locations. We follow this stage with maximum a posteriori (MAP) estimation to eliminate poor candidates and then perform a post-processing operation to remove remaining noise particles. We then fit a thin plate spline (TPS) interpolating surface to the fissure particles to form the final lung lobe segmentation. Results indicate that our algorithm performs comparably to pulmonologist-generated lung lobe segmentations on a set of challenging cases.
This article presents a summary of the key-note lecture delivered at Biomechanics 10 Conference held in August 2010 in Warsaw. We present selected topics in the area of mathematical and numerical modelling of the brain biomechanics for neurosurgical simulation and brain image registration. These processes can reasonably be described in purely mechanical terms, such as displacements, strains and stresses and therefore can be analysed using established methods of continuum mechanics. We advocate the use of fully non-linear theory of continuum mechanics. We discuss in some detail modelling geometry, boundary conditions, loading and material properties. We consider numerical problems such as the use of hexahedral and mixed hexahedral-tetrahedral meshes as well as meshless spatial discretisation schemes. We advocate the use of Total Lagrangian Formulation of both finite element and meshless methods together with explicit time-stepping procedures. We support our recommendations and conclusions with an example of brain shift computation for intraoperative image registration.
We present a model that describes the structure in the responses of different brain areas to a set of stimuli in terms of stimulus categories (clusters of stimuli) and functional units (clusters of voxels). We assume that voxels within a unit respond similarly to all stimuli from the same category, and design a nonparametric hierarchical model to capture inter-subject variability among the units. The model explicitly encodes the relationship between brain activations and fMRI time courses. A variational inference algorithm derived based on the model learns categories, units, and a set of unit-category activation probabilities from data. When applied to data from an fMRI study of object recognition, the method finds meaningful and consistent clusterings of stimuli into categories and voxels into units.
Automatic or semi-automatic segmentation and tracking of artery trees from computed tomography angiography (CTA) is an important step to improve the diagnosis and treatment of artery diseases, but it still remains a significant challenging problem. In this paper, we present an artery extraction method to address the challenge. The proposed method consists of two steps: (1) a geometric moments based tracking to secure a rough centerline, and (2) a fully automatic generalized cylinder structure-based snake method to refine the centerlines and estimate the radii of the arteries. In this method, a new line direction based on first and second order geometric moments is adopted while both gradient and intensity information are used in the snake model to improve the accuracy. The approach has been evaluated on synthetic images as well as 8 clinical coronary CTA images with 32 coronary arteries. Our method achieves 94.7% overlap tracking ability within an average distance inside the vessel of 0.36 mm.
Extracting the prostate from magnetic resonance (MR) imagery is a challenging and important task for medical image analysis and surgical planning. We present in this work a unified shape-based framework to extract the prostate from MR prostate imagery. In many cases, shape-based segmentation is a two-part problem. First, one must properly align a set of training shapes such that any variation in shape is not due to pose. Then segmentation can be performed under the constraint of the learnt shape. However, the general registration task of prostate shapes becomes increasingly difficult due to the large variations in pose and shape in the training sets, and is not readily handled through existing techniques. Thus, the contributions of this paper are twofold. We first explicitly address the registration problem by representing the shapes of a training set as point clouds. In doing so, we are able to exploit the more global aspects of registration via a certain particle filtering based scheme. In addition, once the shapes have been registered, a cost functional is designed to incorporate both the local image statistics as well as the learnt shape prior. We provide experimental results, which include several challenging clinical data sets, to highlight the algorithm's capability of robustly handling supine/prone prostate registration and the overall segmentation task.
We propose algorithms for tracking the boundary contour of a deforming object from an image sequence, when the nonaffine (local) deformation over consecutive frames is large and there is overlapping clutter, occlusions, low contrast, or outlier imagery. When the object is arbitrarily deforming, each, or at least most, contour points can move independently. Contour deformation then forms an infinite (in practice, very large), dimensional space. Direct application of particle filters (PF) for large dimensional problems is impractically expensive. However, in most real problems, at any given time, most of the contour deformation occurs in a small number of dimensions ("effective basis space") while the residual deformation in the rest of the state space ("residual space") is small. This property enables us to apply the particle filtering with mode tracking (PF-MT) idea that was proposed for such large dimensional problems in recent work. Since most contour deformation is low spatial frequency, we propose to use the space of deformation at a subsampled set of locations as the effective basis space. The resulting algorithm is called deform PF-MT. It requires significant modifications compared to the original PF-MT because the space of contours is a non-Euclidean infinite dimensional space.
We present a method for discovering patterns of selectivity in fMRI data for experiments with multiple stimuli/tasks. We introduce a representation of the data as profiles of selectivity using linear regression estimates, and employ mixture model density estimation to identify functional systems with distinct types of selectivity. The method characterizes these systems by their selectivity patterns and spatial maps, both estimated simultaneously via the EM algorithm. We demonstrate a corresponding method for group analysis that avoids the need for spatial correspondence among subjects. Consistency of the selectivity profiles across subjects provides a way to assess the validity of the discovered systems. We validate this model in the context of category selectivity in visual cortex, demonstrating good agreement with the findings based on prior hypothesis-driven methods.
Neuronal currents produce local electromagnetic fields that can potentially modulate the phase of the magnetic resonance signal and thus provide a contrast mechanism tightly linked to neuronal activity. Previous work has demonstrated the feasibility of direct MRI of neuronal activity in phantoms and cell culture, but in vivo efforts have yielded inconclusive, conflicting results. The likelihood of detecting and validating such signals can be increased with (i) fast gradient-echo echo-planar imaging, with acquisition rates sufficient to resolve neuronal activity, (ii) subjects with epilepsy, who frequently experience stereotypical electromagnetic discharges between seizures, expressed as brief, localized, high-amplitude spikes (interictal discharges), and (iii) concurrent electroencephalography. This work demonstrates that both MR magnitude and phase show large-amplitude changes concurrent with electroencephalography spikes. We found a temporal derivative relationship between MR phase and scalp electroencephalography, suggesting that the MR phase changes may be tightly linked to local cerebral activity. We refer to this manner of MR acquisition, designed explicitly to track the electroencephalography, as encephalographic MRI (eMRI). Potential extension of this technique into a general purpose functional neuroimaging tool requires further study of the MR signal changes accompanying lower amplitude neuronal activity than those discussed here.
This paper presents feature-based morphometry (FBM), a new fully data-driven technique for discovering patterns of group-related anatomical structure in volumetric imagery. In contrast to most morphometry methods which assume one-to-one correspondence between subjects, FBM explicitly aims to identify distinctive anatomical patterns that may only be present in subsets of subjects, due to disease or anatomical variability. The image is modeled as a collage of generic, localized image features that need not be present in all subjects. Scale-space theory is applied to analyze image features at the characteristic scale of underlying anatomical structures, instead of at arbitrary scales such as global or voxel-level. A probabilistic model describes features in terms of their appearance, geometry, and relationship to subject groups, and is automatically learned from a set of subject images and group labels. Features resulting from learning correspond to group-related anatomical structures that can potentially be used as image biomarkers of disease or as a basis for computer-aided diagnosis. The relationship between features and groups is quantified by the likelihood of feature occurrence within a specific group vs. the rest of the population, and feature significance is quantified in terms of the false discovery rate. Experiments validate FBM clinically in the analysis of normal (NC) and Alzheimer's (AD) brain images using the freely available OASIS database. FBM automatically identifies known structural differences between NC and AD subjects in a fully data-driven fashion, and an equal error classification rate of 0.80 is achieved for subjects aged 60-80 years exhibiting mild AD (CDR=1).
We propose a technique to simultaneously estimate the local fiber orientations and perform multi-fiber tractography. Existing techniques estimate the local fiber orientation at each voxel independently so there is no running knowledge of confidence in the measured signal or estimated fiber orientation. Further, to overcome noise, many algorithms use a filter as a post-processing step to obtain a smooth trajectory. We formulate fiber tracking as causal estimation: at each step of tracing the fiber, the current estimate of the signal is guided by the previous. To do this, we model the signal as a discrete mixture of Watson directional functions and perform tractography within a filtering framework. Starting from a seed point, each fiber is traced to its termination using an unscented Kalman filter to simultaneously fit the signal and propagate in the most consistent direction. Despite the presence of noise and uncertainty, this provides an accurate estimate of the local structure at each point along the fiber. We choose the Watson function since it provides a compact representation of the signal parameterized by the principal diffusion direction and a scaling parameter describing anisotropy, and also allows analytic reconstruction of the oriented diffusion function from those parameters. Using a mixture of two and three components (corresponding to two-fiber and three-fiber models) we demonstrate in synthetic experiments that this approach reduces signal reconstruction error and significantly improves the angular resolution at crossings and branchings. In vivo experiments examine the corpus callosum and internal capsule and confirm the ability to trace through regions known to contain such crossing and branching while providing inherent path regularization.
We describe a technique that uses tractography to drive the local fiber model estimation. Existing techniques use independent estimation at each voxel so there is no running knowledge of confidence in the estimated model fit. We formulate fiber tracking as recursive estimation: at each step of tracing the fiber, the current estimate is guided by those previous. To do this we perform tractography within a filter framework and use a discrete mixture of Gaussian tensors to model the signal. Starting from a seed point, each fiber is traced to its termination using an unscented Kalman filter to simultaneously fit the local model to the signal and propagate in the most consistent direction. Despite the presence of noise and uncertainty, this provides a causal estimate of the local structure at each point along the fiber. Using two- and three-fiber models we demonstrate in synthetic experiments that this approach significantly improves the angular resolution at crossings and branchings. In vivo experiments confirm the ability to trace through regions known to contain such crossing and branching while providing inherent path regularization.
BACKGROUND: Total subcutaneous implantable subcutaneous defibrillators are in development, but optimal electrode configurations are not known.
OBJECTIVE: We used image-based finite element models (FEM) to predict the myocardial electric field generated during defibrillation shocks (pseudo-DFT) in a wide variety of reported and innovative subcutaneous electrode positions to determine factors affecting optimal lead positions for subcutaneous implantable cardioverter-defibrillators (S-ICD).
METHODS: An image-based FEM of an adult man was used to predict pseudo-DFTs across a wide range of technically feasible S-ICD electrode placements. Generator location, lead location, length, geometry and orientation, and spatial relation of electrodes to ventricular mass were systematically varied. Best electrode configurations were determined, and spatial factors contributing to low pseudo-DFTs were identified using regression and general linear models.
RESULTS: A total of 122 single-electrode/array configurations and 28 dual-electrode configurations were simulated. Pseudo-DFTs for single-electrode orientations ranged from 0.60 to 16.0 (mean 2.65 +/- 2.48) times that predicted for the base case, an anterior-posterior configuration recently tested clinically. A total of 32 of 150 tested configurations (21%) had pseudo-DFT ratios
The corticospinal tract (CST) is one of the most well studied tracts in human neuroanatomy. Its clinical significance can be demonstrated in many notable traumatic conditions and diseases such as stroke, spinal cord injury (SCI) or amyotrophic lateral sclerosis (ALS). With the advent of diffusion MRI and tractography the computational representation of the human CST in a 3D model became available. However, the representation of the entire CST and, specifically, the hand motor area has remained elusive. In this paper we propose a novel method, using manually drawn ROIs based on robustly identifiable neuroanatomic structures to delineate the entire CST and isolate its hand motor representation as well as to estimate their variability and generate a database of their volume, length and biophysical parameters. Using 37 healthy human subjects we performed a qualitative and quantitative analysis of the CST and the hand-related motor fiber tracts (HMFTs). Finally, we have created variability heat maps from 37 subjects for both the aforementioned tracts, which could be utilized as a reference for future studies with clinical focus to explore neuropathology in both trauma and disease states.
BACKGROUND: Extracellular free water within cerebral white matter tissue has been shown to increase with age and pathology, yet the cognitive consequences of free water in typical aging prior to the development of neurodegenerative disease remains unclear. Understanding the contribution of free water to cognitive function in older adults may provide important insight into the neural mechanisms of the cognitive aging process. METHODS: A diffusion-weighted MRI measure of extracellular free water as well as a commonly used diffusion MRI metric (fractional anisotropy) along nine bilateral white matter pathways were examined for their relationship with cognitive function assessed by the NIH Toolbox Cognitive Battery in 47 older adults (mean age = 74.4 years, SD = 5.4 years, range = 65-85 years). Probabilistic tractography at the 99th percentile level of probability (Tracts Constrained by Underlying Anatomy; TRACULA) was utilized to produce the pathways on which microstructural characteristics were overlaid and examined for their contribution to cognitive function independent of age, education, and gender. RESULTS: When examining the 99th percentile probability core white matter pathway derived from TRACULA, poorer fluid cognitive ability was related to higher mean free water values across the angular and cingulum bundles of the cingulate gyrus, as well as the corticospinal tract and the superior longitudinal fasciculus. There was no relationship between cognition and mean FA or free water-adjusted FA across the 99th percentile core white matter pathway. Crystallized cognitive ability was not associated with any of the diffusion measures. When examining cognitive domains comprising the NIH Toolbox Fluid Cognition index relationships with these white matter pathways, mean free water demonstrated strong hemispheric and functional specificity for cognitive performance, whereas mean FA was not related to age or cognition across the 99th percentile pathway. CONCLUSIONS: Extracellular free water within white matter appears to increase with normal aging, and higher values are associated with significantly lower fluid but not crystallized cognitive functions. When using TRACULA to estimate the core of a white matter pathway, a higher degree of free water appears to be highly specific to the pathways associated with memory, working memory, and speeded decision-making performance, whereas no such relationship existed with FA. These data suggest that free water may play an important role in the cognitive aging process, and may serve as a stronger and more specific indicator of early cognitive decline than traditional diffusion MRI measures, such as FA.
RATIONALE AND OBJECTIVES: To explore a role for multiparametric MRI (mpMRI) as a biomarker of response to neoadjuvant androgen deprivation therapy (ADT) for prostate cancer (PCa).
MATERIALS AND METHODS: This prospective study was approved by the institutional review board and was HIPAA compliant. Eight patients with localized PCa had a baseline mpMRI, repeated after 6-months of ADT, followed by prostatectomy. mpMRI indices were extracted from tumor and normal regions of interest (TROI/NROI). Residual cancer burden (RCB) was measured on mpMRI and on the prostatectomy specimen. Paired t-tests compared TROI/NROI mpMRI indices and pre/post-treatment TROI mpMRI indices. Spearman's rank tested for correlations between MRI/pathology-based RCB, and between pathological RCB and mpMRI indices.
RESULTS: At baseline, TROI apparent diffusion coefficient (ADC) was lower and dynamic contrast enhanced (DCE) metrics were higher, compared to NROI (ADC: 806 ± 137 × 10 vs. 1277 ± 213 × 10 mm/sec, p = 0.0005; K: 0.346 ± 0.16 vs. 0.144 ± 0.06 min, p = 0.002; AUC: 0.213 ± 0.08 vs. 0.11 ± 0.03, p = 0.002). Post-treatment, there was no change in TROI ADC, but a decrease in TROI K (0.346 ± 0.16 to 0.188 ± 0.08 min; p = 0.02) and AUC (0.213 ± 0.08 to 0.13 ± 0.06; p = 0.02). Tumor volume decreased with ADT. There was no difference between mpMRI-based and pathology-based RCB, which positively correlated (⍴ = 0.74-0.81, p < 0.05). Pathology-based RCB positively correlated with post-treatment DCE metrics (⍴ = 0.76-0.70, p < 0.05) and negatively with ADC (⍴ = -0.79, p = 0.03).
CONCLUSION: Given the heterogeneity of PCa, an individualized approach to ADT may maximize potential benefit. This pilot study suggests that mpMRI may serve as a biomarker of ADT response and as a surrogate for RCB at prostatectomy.
INTRODUCTION: Before using blood-oxygen-level-dependent magnetic resonance imaging (BOLD MRI) during maternal hyperoxia as a method to detect individual placental dysfunction, it is necessary to understand spatiotemporal variations that represent normal placental function. We investigated the effect of maternal position and Braxton-Hicks contractions on estimates obtained from BOLD MRI of the placenta during maternal hyperoxia. METHODS: For 24 uncomplicated singleton pregnancies (gestational age 27-36 weeks), two separate BOLD MRI datasets were acquired, one in the supine and one in the left lateral maternal position. The maternal oxygenation was adjusted as 5 min of room air (21% O), followed by 5 min of 100% FiO. After datasets were corrected for signal non-uniformities and motion, global and regional BOLD signal changes in R* and voxel-wise Time-To-Plateau (TTP) in the placenta were measured. The overall placental and uterine volume changes were determined across time to detect contractions. RESULTS: In mothers without contractions, increases in global placental R* in the supine position were larger compared to the left lateral position with maternal hyperoxia. Maternal position did not alter global TTP but did result in regional changes in TTP. 57% of the subjects had Braxton-Hicks contractions and 58% of these had global placental R* decreases during the contraction. CONCLUSION: Both maternal position and Braxton-Hicks contractions significantly affect global and regional changes in placental R* and regional TTP. This suggests that both factors must be taken into account in analyses when comparing placental BOLD signals over time within and between individuals.
We investigated brain wiring in chronic schizophrenia and healthy controls in frontostriatal circuits using diffusion magnetic resonance imaging tractography in a novel way. We extracted diffusion streamlines in 27 chronic schizophrenia and 26 healthy controls connecting 4 frontal subregions to the striatum. We labeled the projection zone striatal surface voxels into 2 subtypes: dominant-input from a single cortical subregion, and, functionally integrative, with mixed-input from diverse cortical subregions. We showed: 1) a group difference for total striatal surface voxel number (P = .045) driven by fewer mixed-input voxels in the left (P = .007), but not right, hemisphere; 2) a group by hemisphere interaction for the ratio quotient between voxel subtypes (P = .04) with a left (P = .006), but not right, hemisphere increase in schizophrenia, also reflecting fewer mixed-input voxels; and 3) fewer mixed-input voxel counts in schizophrenia (P = .045) driven by differences in left hemisphere limbic (P = .007) and associative (P = .01), but not sensorimotor, striatum. These results demonstrate a less integrative pattern of frontostriatal structural connectivity in chronic schizophrenia. A diminished integrative pattern yields a less complex input pattern to the striatum from the cortex with less circuit integration at the level of the striatum. Further, as brain wiring occurs during early development, aberrant brain wiring could serve as a developmental biomarker for schizophrenia.