Imitation strategies in subjects with schizophrenia: a behavioural approach.

Imitation is a basic human ability, present early in life. Previous studies on control subjects and callosotomized patients showed that imitation occurred mainly in mirror-mode in both groups (60% controls, 66% patients) when they imitate without instructions (free sessions). In contrast, when asked to use the same or opposite limb as the model (driven sessions), controls used anatomical mode (93%), callosotomized patients mainly mirror strategy (61%). It has been suggested that callosotomized subjects prefer the mirror mode because of an impaired capacity for mental rotation, likely due to the lack of the corpus callosum (CC). The present research investigated the imitation strategies used by schizophrenic patients, who also could present anomaly in the interhemispheric connections. Fifteen hospitalized patients with diagnosis of schizophrenia participated in the study. They were asked to imitate upper limb intransitive meaningful and meaningless gestures performed by a model in a video. The results were compared with those from 20 healthy individuals. In driven imitation, controls answered in anatomical mode (95% of the responses), versus 63% of patients' responses. In free imitation sessions the answers in anatomical mode decreased to 39% in control subjects and to 46% in schizophrenic patients. In both driven and free imitation, the differences between the two proportions, conditioned to Diagnosis, resulted significantly different. The present data, in line with previous studies on psychotic and neurological patients showing impairments on imitation, suggest that the neural circuitry leading patients to perform differently from controls likely relates with the functional efficiency of the CC.

Imitation Strategies in Callosotomized Patients.

Imitation is a human ability rooted in early life. It allows people to interact with each other by observing and reproducing simple and complex movements alike. Imitation can occur in at least two forms: the rst, de ned as anatomical, seems to be based primarily on the mental construct of the "body schema" because the imitating movement corresponds precisely to the imitated movement in bodily terms, but not in terms of spatial compatibility. For example, a right arm movement of a model is imitated with a right arm movement by a facing imitator in a spatially incompatible fashion. The other form, de ned as specular or mirror-mode, involves a spatially compatible matching between imitated and imitating movements, as when an imitator moves her right arm upon viewing a corresponding left arm movement of a facing model (Chiavarino et al., 2007). In a previous study, healthy subjects showed a slight (61%) preference for the specular mode when freely imitating meaningful and meaningless gestures, whereas they strongly preferred the anatomical mode (93%) when given an intentionally ambiguous instruction such as "use the same (or the opposite) limb as the model" (Pierpaoli et al., 2014). In the present investigation it has been shown that callosotomized patients tended to favour the mirror-mode in both the free (66%) and the instructed condition (61% responses in driven sessions) regardless instructions given by the experimenter. Moreover, present data suggest that the extent of the callosotomy may in uence the patient's performance.

Defining an Analytic Framework to Evaluate Quantitative MRI Markers of Traumatic Axonal Injury: Preliminary Results in a Mouse Closed Head Injury Model.

Diffuse axonal injury (DAI) is a hallmark of traumatic brain injury (TBI) pathology. Recently, the Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA) was developed to generate an experimental model of DAI in a mouse. The characterization of DAI using diffusion tensor magnetic resonance imaging (MRI; diffusion tensor imaging, DTI) may provide a useful set of outcome measures for preclinical and clinical studies. The objective of this study was to identify the complex neurobiological underpinnings of DTI features following DAI using a comprehensive and quantitative evaluation of DTI and histopathology in the CHIMERA mouse model. A consistent neuroanatomical pattern of pathology in specific white matter tracts was identified across ex vivo DTI maps and photomicrographs of histology. These observations were confirmed by voxelwise and regional analysis of DTI maps, demonstrating reduced fractional anisotropy (FA) in distinct regions such as the optic tract. Similar regions were identified by quantitative histology and exhibited axonal damage as well as robust gliosis. Additional analysis using a machine-learning algorithm was performed to identify regions and metrics important for injury classification in a manner free from potential user bias. This analysis found that diffusion metrics were able to identify injured brains almost with the same degree of accuracy as the histology metrics. Good agreement between regions detected as abnormal by histology and MRI was also found. The findings of this work elucidate the complexity of cellular changes that give rise to imaging abnormalities and provide a comprehensive and quantitative evaluation of the relative importance of DTI and histological measures to detect brain injury.

Population based MRI and DTI templates of the adult ferret brain and tools for voxelwise analysis.

Non-invasive imaging has the potential to play a crucial role in the characterization and translation of experimental animal models to investigate human brain development and disorders, especially when employed to study animal models that more accurately represent features of human neuroanatomy. The purpose of this study was to build and make available MRI and DTI templates and analysis tools for the ferret brain as the ferret is a well-suited species for pre-clinical MRI studies with folded cortical surface, relatively high white matter volume and body dimensions that allow imaging with pre-clinical MRI scanners. Four ferret brain templates were built in this study - in-vivo MRI and DTI and ex-vivo MRI and DTI - using brain images across many ferrets and region of interest (ROI) masks corresponding to established ferret neuroanatomy were generated by semi-automatic and manual segmentation. The templates and ROI masks were used to create a web-based ferret brain viewing software for browsing the MRI and DTI volumes with annotations based on the ROI masks. A second objective of this study was to provide a careful description of the imaging methods used for acquisition, processing, registration and template building and to demonstrate several voxelwise analysis methods including Jacobian analysis of morphometry differences between the female and male brain and bias-free identification of DTI abnormalities in an injured ferret brain. The templates, tools and methodological optimization presented in this study are intended to advance non-invasive imaging approaches for human-similar animal species that will enable the use of pre-clinical MRI studies for understanding and treating brain disorders.

Whole-Brain DTI Assessment of White Matter Damage in Children with Bilateral Cerebral Palsy: Evidence of Involvement beyond the Primary Target of the Anoxic Insult.

BACKGROUND AND PURPOSE: Cerebral palsy is frequently associated with both motor and nonmotor symptoms. DTI can characterize the damage at the level of motor tracts but provides less consistent results in nonmotor areas. We used a standardized pipeline of analysis to describe and quantify the pattern of DTI white matter abnormalities of the whole brain in a group of children with chronic bilateral cerebral palsy and periventricular leukomalacia. We also explored potential correlations between DTI and clinical scale metrics. MATERIALS AND METHODS: Twenty-five patients (mean age, 11.8 years) and 25 healthy children (mean age, 11.8 years) were studied at 3T with a 2-mm isotropic DTI sequence. Differences between patients and controls were assessed both voxelwise and in ROIs obtained from an existing DTI atlas. Clinical metrics included the Gross Motor Function Classification System, the Manual Ability Classification System, and intelligence quotient. RESULTS: The voxel-level and ROI-level analyses demonstrated highly significant (P < .001) modifications of DTI measurements in patients at several levels: cerebellar peduncles, corticospinal tracts and posterior thalamic radiations, posterior corpus callosum, external capsule, anterior thalamic radiation, superior longitudinal fasciculi and corona radiata, optic nerves, and chiasm. The reduction of fractional anisotropy values in significant tracts was between 8% and 30%. Statistically significant correlations were found between motor impairment and fractional anisotropy in corticospinal tracts and commissural and associative tracts of the supratentorial brain. CONCLUSIONS: We demonstrated the involvement of several motor and nonmotor areas in the chronic damage associated with periventricular leukomalacia and showed new correlations between motor skills and DTI metrics.

Further evidence for the topography and connectivity of the corpus callosum: an FMRI study of patients with partial callosal resection.

BACKGROUND AND PURPOSE: This functional MRI study was designed to describe activated fiber topography and trajectories in the corpus callosum (CC) of six patients carrying different degree of partial callosal resection. METHODS: Patients receiving gustatory, tactile, and visual stimulation according to a block-design protocol were scanned in a 1.5 Tesla magnet. Diffusion tensor imaging (DTI) data were also acquired to visualize spared interhemispheric fibers. RESULTS: Taste stimuli evoked bilateral activation of the primary gustatory area in all patients and foci in the anterior CC, when spared. Tactile stimuli to the hand evoked bilateral foci in the primary somatosensory area in patients with an intact posterior callosal body and only contralateral in the other patients. Callosal foci occurred in the CC body, if spared. In patients with an intact splenium central visual stimulation induced bilateral activation of the primary visual area as well as foci in the splenium itself. CONCLUSION: Present data show that interhemispheric fibers linking sensory areas crossed through the CC at the sites where the different sensory stimuli evoked activation foci, and that topography of callosal foci evoked by sensory stimulation in spared CC portions is consistent with that previously observed in subjects with intact CC.

Anatomical or mirror mode imitation? A behavioral approach.

Imitation can occur in at least two forms: one, which can be defined as anatomical, is based primarily on the mental construct of the body schema and allows recognition of correspondences between own body anatomy and that of other individuals. The other form, defined as specular or mirror mode, is most probably based on the allocation of some form of attention to the same region of the environmental space both by model and imitator, and to the objects it contains. This study investigated the behavioral strategy of imitation in normal subjects, to assess whether they carried out task instructions using an anatomical or a mirror perspective. Twenty seven adults were asked to imitate intransitive meaningful and meaningless gestures shown by a model in video clips. Instructions about how to perform them were provided before each trial. Trials were free (intended to produce spontaneous imitation) or driven (intended to produce anatomical imitation); further driven trials were administered to verify participants' knowledge of bodily laterality and were used as control. Performances were interpreted as anatomical or mirror imitation, according to the observation of anatomical or spatial reference frames between stimulus and imitator. The results revealed that in spontaneous imitation the mirror mode was more frequent (61% of responses), in line with previous studies. The novel finding was the prevalence (93% of responses) of anatomical imitation in tasks involving detailed driven instructions.

Susceptibility distortion correction for echo planar images with non-uniform B-spline grid sampling: a diffusion tensor image study.

In this paper, we propose a novel method for correcting the geometric distortions in diffusion weighted images (DWI) obtained with echo planar imaging (EPI) protocol. Our EPI distortion correction approach employs a deformable registration framework with the B-splines transformation, where the control point distributions are non-uniform and functions of the expected norm of the spatial distortions. In our framework, the amount of distortions are first computed by estimating the B(0) fieldmap from an initial segmentation of a distortion-free structural image and tissue susceptibility models. Fieldmap estimates are propagated to obtain expected spatial distortion maps, which are used in the sampling of active B-spline control points. This transformation is flexible in locations with large distortion expectations, yet with relatively few degrees-of-freedom and does not suffer from local optima convergence and hence does not distort anatomically salient locations. Results indicate that with the proposed correction scheme, tensor derived scalar maps and fiber tracts of the same subject computed from data acquired with different phase encoding directions provide better coherency and consistency compared traditional registration based approaches.

Comparison of EPI distortion correction methods in diffusion tensor MRI using a novel framework.

Diffusion weighted images (DWIs) are commonly acquired with Echo-planar imaging (EPI). B0 inhomogeneities affect EPI by producing spatially nonlinear image distortions. Several strategies have been proposed to correct EPI distortions including B0 field mapping (B0M) and image registration. In this study, an experimental framework is proposed to evaluation the performance of different EPI distortion correction methods in improving DT-derived quantities. A deformable registration based method with mutual information metric and cubic B-spline modeled constrained deformation field (BSP) is proposed as an alternative when B0 mapping data are not available. BSP method is qualitatively and quantitatively compared to B0M method using the framework. Both methods can successful reduce EPI distortions and significantly improve the quality of DT-derived quantities. Overall, B0M was clearly superior in infratentorial regions including brainstem and cerebellum, as well as in the ventral areas of the temporal lobes while BSP was better in all rostral brain regions.

Automatic deformable diffusion tensor registration for fiber population analysis.

In this work, we propose a novel method for deformable tensor-to-tensor registration of Diffusion Tensor Images. Our registration method models the distances in between the tensors with Geode-sic-Loxodromes and employs a version of Multi-Dimensional Scaling (MDS) algorithm to unfold the manifold described with this metric. Defining the same shape properties as tensors, the vector images obtained through MDS are fed into a multi-step vector-image registration scheme and the resulting deformation fields are used to reorient the tensor fields. Results on brain DTI indicate that the proposed method is very suitable for deformable fiber-to-fiber correspondence and DTI-atlas construction.

Comprehensive approach for correction of motion and distortion in diffusion-weighted MRI.

Patient motion and image distortion induced by eddy currents cause artifacts in maps of diffusion parameters computed from diffusion-weighted (DW) images. A novel and comprehensive approach to correct for spatial misalignment of DW imaging (DWI) volumes acquired with different strengths and orientations of the diffusion sensitizing gradients is presented. This approach uses a mutual information-based registration technique and a spatial transformation model containing parameters that correct for eddy current-induced image distortion and rigid body motion in three dimensions. All parameters are optimized simultaneously for an accurate and fast solution to the registration problem. The images can also be registered to a normalized template with a single interpolation step without additional computational cost. Following registration, the signal amplitude of each DWI volume is corrected to account for size variations of the object produced by the distortion correction, and the b-matrices are properly recalculated to account for any rotation applied during registration. Both qualitative and quantitative results show that this approach produces a significant improvement of diffusion tensor imaging (DTI) data acquired in the human brain.

Spatial transformations of diffusion tensor magnetic resonance images.

We address the problem of applying spatial transformations (or "image warps") to diffusion tensor magnetic resonance images. The orientational information that these images contain must be handled appropriately when they are transformed spatially during image registration. We present solutions for global transformations of three-dimensional images up to 12-parameter affine complexity and indicate how our methods can be extended for higher order transformations. Several approaches are presented and tested using synthetic data. One method, the preservation of principal direction algorithm, which takes into account shearing, stretching and rigid rotation, is shown to be the most effective. Additional registration experiments are performed on human brain data obtained from a single subject, whose head was imaged in three different orientations within the scanner. All of our methods improve the consistency between registered and target images over naïve warping algorithms.

Water diffusion changes in Wallerian degeneration and their dependence on white matter architecture.

This study investigates water diffusion changes in Wallerian degeneration. We measured indices derived from the diffusion tensor (DT) and T2-weighted signal intensities in the descending motor pathways of patients with small chronic lacunar infarcts of the posterior limb of the internal capsule on one side. We compared these measurements in the healthy and lesioned sides at different levels in the brainstem caudal to the primary lesion. We found that secondary white matter degeneration is revealed by a large reduction in diffusion anisotropy only in regions where fibers are arranged in isolated bundles of parallel fibers, such as in the cerebral peduncle. In regions where the degenerated pathway crosses other tracts, such as in the rostral pons, paradoxically there is almost no change in diffusion anisotropy, but a significant change in the measured orientation of fibers. The trace of the diffusion tensor is moderately increased in all affected regions. This allows one to differentiate secondary and primary fiber loss where the increase in trace is considerably higher. We show that DT-MRI is more sensitive than T2-weighted MRI in detecting Wallerian degeneration. Significant diffusion abnormalities are observed over the entire trajectory of the affected pathway in each patient. This finding suggests that mapping degenerated pathways noninvasively with DT-MRI is feasible. However, the interpretation of water diffusion data is complex and requires a priori information about anatomy and architecture of the pathway under investigation. In particular, our study shows that in regions where fibers cross, existing DT-MRI-based fiber tractography algorithms may lead to erroneous conclusion about brain connectivity.

In vivo fiber tractography using DT-MRI data.

Fiber tract trajectories in coherently organized brain white matter pathways were computed from in vivo diffusion tensor magnetic resonance imaging (DT-MRI) data. First, a continuous diffusion tensor field is constructed from this discrete, noisy, measured DT-MRI data. Then a Frenet equation, describing the evolution of a fiber tract, was solved. This approach was validated using synthesized, noisy DT-MRI data. Corpus callosum and pyramidal tract trajectories were constructed and found to be consistent with known anatomy. The method's reliability, however, degrades where the distribution of fiber tract directions is nonuniform. Moreover, background noise in diffusion-weighted MRIs can cause a computed trajectory to hop from tract to tract. Still, this method can provide quantitative information with which to visualize and study connectivity and continuity of neural pathways in the central and peripheral nervous systems in vivo, and holds promise for elucidating architectural features in other fibrous tissues and ordered media.

Color schemes to represent the orientation of anisotropic tissues from diffusion tensor data: application to white matter fiber tract mapping in the human brain.

This paper investigates the use of color to represent the directional information contained in the diffusion tensor. Ideally, one wants to take into account both the properties of human color vision and of the given display hardware to produce a representation in which differences in the orientation of anisotropic structures are proportional to the perceived differences in color. It is argued here that such a goal cannot be achieved in general and therefore, empirical or heuristic schemes, which avoid some of the common artifacts of previously proposed approaches, are implemented. Directionally encoded color (DEC) maps of the human brain obtained using these schemes clearly show the main association, projection, and commissural white matter pathways. In the brainstem, motor and sensory pathways are easily identified and can be differentiated from the transverse pontine fibers and the cerebellar peduncles. DEC maps obtained from diffusion tensor imaging data provide a simple and effective way to visualize fiber direction, useful for investigating the structural anatomy of different organs. Magn Reson Med 42:526-540, 1999.

Visualizing and characterizing white matter fiber structure and architecture in the human pyramidal tract using diffusion tensor MRI.

We used diffusion tensor imaging to assess diffusion anisotropy in the pyramidal tract in ten young, and ten elderly subjects (five males and five females in each group). The purpose of this study was to define normative values for anisotropy at different anatomic levels of the brainstem as well as to assess differences due to age, gender, and laterality. In all subjects, anisotropy was highest in the cerebral peduncle, lowest in the caudal pons, and intermediate in the medulla. In the pons and medulla the regional variability was high, with significant differences in anisotropy even between contiguous slices. Multifactorial ANOVA (performed using the average value of anisotropy within each region of interest) revealed that elderly subjects had significantly lower values than young subjects in the cerebral peduncle, with no differences in the pons and medulla. No significant differences in anisotropy due to gender and side were found. The differences in anisotropy at different levels of the brainstem reflect differences in the local architecture of white matter fibers. Anisotropy is high in the cerebral peduncle because fibers have a highly ordered arrangement, while in the pons and medulla, anisotropy is lower because the local fiber architecture is less coherent due to the presence of other fibers and nuclei. The biologic meaning of the intergroup differences in anisotropy is discussed in light of the structure and architecture of the tissue under investigation. We also consider potential sources of artifacts, such as noise and motion, partial volume contamination, anatomic mismatching, and the use of inappropriate statistical tests. We conclude that the age-related decrease in anisotropy in the cerebral peduncle is not artifactual but rather reflects subtle structural changes of the aging white matter. Our study however shows that caution must be exercised in interpreting diffusion anisotropy data.

Comparative MR imaging study of brain maturation in kittens with T1, T2, and the trace of the diffusion tensor.

PURPOSE: To assess the time-course of the relaxation times and the orientationally averaged water diffusion coefficient Doav in postnatal brain development. MATERIALS AND METHODS: Multisection maps of T1, T2, and the trace of the diffusion tensor (Trace[D] = 3 x Doav) were obtained in four kittens at eight time points. RESULTS: In the adult, Doav was about 700 micron 2/sec in both white and gray matter. In the newborn, Doav was 1,100-1,350 micron 2/sec in white matter and 1,000 micron 2/sec in gray matter. For all anatomic regions and time points, the correlation between Doav and 1/T2 was high (R2 = 0.87, P << .001). T1 showed a lower correlation with Doav and a higher sensitivity to myelinization than did T2. CONCLUSION: Although Doav shows dramatic changes in the maturing brain, the high correlation between Doav and T2 indicates that little additional information can be obtained by measuring this diffusion parameter during normal brain development. This contrasts with previous findings in brain ischemia, where Doav and T2 appear to be uncorrelated. After including the authors' data and published iontophoretic measurements in a simple model of diffusion in tissues, the authors suggest that the underlying mechanisms of Doav reduction in brain maturation and ischemia are different. Doav changes during development are mainly affected by events occurring in the cellular compartment, while changes in extracellular volume fraction and tortuosity, which are thought to determine the reduction in Doav during ischemia, are probably of secondary importance.

A simplified method to measure the diffusion tensor from seven MR images.

Analytical expressions of the diffusion tensor of water, D, and of scalar invariants derived from it, are given in terms of the intensities of seven diffusion-weighted images (DWIs). These formulas simplify the post-processing steps required in diffusion tensor imaging, including estimating D in each voxel (from the set of b-matrices and their corresponding DWIs), and then computing its eigenvalues, eigenvectors, and scalar invariants. In a study conducted using artifact-free DWIs with high diffusion weighting (bmax approximately 900 s/mm2, maps of Trace(D) and the Relative and Lattice Anisotropy indices calculated analytically and by multivariate linear regression showed excellent agreement in brain parenchyma of a healthy living cat. However, the quality of the analytically computed maps degraded markedly as diffusion weighting was reduced. Although diffusion tensor MRI with seven DWIs may be useful for clinical applications where rapid scanning and data processing are required, it does not provide estimates of the uncertainty of the measured imaging parameters, rendering it susceptible to noise and systematic artifacts. Therefore, care should be taken when using this technique in radiological applications.

Characterization of and correction for eddy current artifacts in echo planar diffusion imaging.

Magnetic resonance diffusion imaging is potentially an important tool for the noninvasive characterization of normal and pathological tissue. The technique, however, is prone to a number of artifacts that can severely affect its ability to provide clinically useful information. In this study, the problem of eddy current-induced geometric distortions that occur in diffusion images acquired with echo planar sequences was addressed. These geometric distortions produce artifacts in computed maps of diffusion parameters and are caused by misalignments in the individual diffusion-weighted images that comprise the diffusion data set. A new approach is presented to characterize and calibrate the eddy current effects, enabling the eddy current distortions to be corrected in sets of interleaved (or snapshot) echo planar diffusion images. Correction is achieved by acquiring one-dimensional field maps in the read and phase encode direction for each slice and each diffusion step. The method is then demonstrated through the correction of distortions in diffusion images of the human brain. It is shown that by using the eddy current correction scheme outlined, the eddy current-induced artifacts in the diffusion-weighted images are almost completely eliminated. In addition, there is a significant improvement in the quality of the resulting diffusion tensor maps.