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In this retrospective study we tested the hypothesis that the net effect of impaired electrical conduction and therefore increased heat dissipation in multiple sclerosis (MS) results in elevated lateral ventricular (LV) cerebrospinal fluid (CSF) diffusivity as a measure of brain temperature estimated in vivo using diffusion tensor imaging (DTI). We used validated DTI-based segmentation methods to obtain normalized LV-CSF volume and its corresponding CSF diffusivity in 108 MS patients and 103 healthy controls in the age range of 21–63 years. The LV CSF diffusivity was ~ 2% higher in MS compared to controls that correspond to a temperature rise of ~ 1 °C that could not be explained by changes in the CSF viscosity due to altered CSF protein content in MS. The LV diffusivity decreased with age in healthy controls (r = − 0.29; p = 0.003), but not in MS (r = 0.15; p = 0.11), possibly related to MS pathology. Age-adjusted LV diffusivity increased with lesion load (r = 0.518; p = 1 × 10 − 8 ). Our data suggest that the total brain lesion load is the primary contributor to the increase in LV CSF diffusivity in MS. These findings suggest that LV diffusivity is a potential in vivo biomarker of the mismatch between heat generation and dissipation in MS. We also discuss limitations and possible confounders. [ABSTRACT FROM AUTHOR]

Quantification of the living human visual system using MRI methods has been challenging, but several applications demand a reliable and time-efficient data acquisition protocol. In this study, we demonstrate the utility of high-spatial-resolution diffusion tensor fiber tractography (DTT) in reconstructing and quantifying the human visual pathways. Five healthy males, age range 24-37 years, were studied after approval of the institutional review board (IRB) at The University of Texas Health Science Center at Houston. We acquired diffusion tensor imaging (DTI) data with 1-mm slice thickness on a 3.0-Tesla clinical MRI scanner and analyzed the data using DTT with the fiber assignment by continuous tractography (FACT) algorithm. By utilizing the high-spatial-resolution DTI protocol with FACT algorithm, we were able to reconstruct and quantify bilateral optic pathways including the optic chiasm, optic tract, optic radiations free of contamination from neighboring white matter tracts. [ABSTRACT FROM AUTHOR]

Abstract: The human brain lateral ventricular (LV) cerebrospinal fluid (CSF) volume has been used as a neuroimaging marker of brain changes in health and disease. The LV CSF diffusivity may offer a useful quality assurance measure and become a potential noninvasive marker of deep brain temperature. In this work we sought to validate a method for human brain lateral ventricular (LV) cerebrospinal fluid (CSF) using diffusion tensor imaging (DTI) contrast to provide LV volume and corresponding DTI metrics. We compared LV volume obtained using DTI with that obtained using validated segmentations of the LV on T1-weighted data. DTI and T1-weighted data were acquired at 3T on 49 healthy males and 56 age-matched females aged 18–59years. We showed histogram distributions of LV DTI metrics to establish quality assurance measures. We also analyzed the age and gender effects of LV volume and diffusivity. LV volumes estimated using both T1-weighted and DTI correlated strongly in males and females (ICC=0.99; median Dice index ~80%). The LV-to-intracranial volume percentage increased significantly with age only in males, using the DTI-based approach (r=0.39; p=0.005). LV CSF Mean diffusivity was greater in males than females ((~1.2%; p=0.03). Mean diffusivity of lateral ventricular CSF decreased significantly with age in healthy adults (r=−0.30; p=0.02). Our results highlight the importance of age and gender-based analyses and the potential of LV diffusivity measures as a quantitative marker. [Copyright &y& Elsevier]

Abstract: Accurate and noninvasive quantification of regional cerebral blood perfusion (CBF) of the human brain tissue would advance the study of the complex interplay between human brain structure and function, in both health and disease. Despite the plethora of works on CBF in gray matter, a detailed quantitative white matter perfusion atlas has not been presented on healthy adults using the International Consortium for Brain Mapping atlases. In this study, we present a host of assurance measures such as temporal stability, spatial heterogeneity and age effects of regional and global CBF in selected deep, cortical gray matter and white matter tracts identified and quantified using diffusion tensor imaging (DTI). We utilized whole brain high-resolution DTI combined with arterial spin labeling to quantify regional CBF on 15 healthy adults aged 23.2–57.1years. We present total brain and regional CBF, corresponding volume, mean diffusivity and fractional anisotropy spatial heterogeneity, and dependence on age as additional quality assurance measures to compare with published trends using both MRI and nuclear medicine methods. Total CBF showed a steady decrease with age in gray matter (r=−0.58; P=.03), whereas total CBF of white matter did not significantly change with age (r=0.11; P=.7). This quantitative report offers a preliminary baseline of CBF, volume and DTI measurements for the design of future multicenter and clinical studies utilizing noninvasive perfusion and DT-MRI. [Copyright &y& Elsevier]

Abstract: Multiple sclerosis (MS) is the most common immune-mediated disabling neurological disease of the central nervous system. The pathogenesis of MS is not fully understood. Histopathology implicates both demyelination and axonal degeneration as the major contributors to the accumulation of disability. The application of several in vivo quantitative magnetic resonance imaging (MRI) methods to both lesioned and normal-appearing brain tissue has not yet provided a solid conclusive support of the hypothesis that MS might be a diffuse disease. In this work, we adopted FreeSurfer to provide standardized macrostructure or volumetry of lesion free normal-appearing brain tissue in combination with multiple quantitative MRI metrics (T2 relaxation time, diffusion tensor anisotropy and diffusivities) that characterize tissue microstructural integrity. By incorporating a large number of healthy controls, we have attempted to separate the natural age-related change from the disease-induced effects. Our work shows elevation in diffusivity and relaxation times and reduction in volume in a number of normal-appearing white matter and gray matter structures in relapsing–remitting multiple sclerosis patients. These changes were related in part with the spatial distribution of lesions. The whole brain lesion load and age-adjusted expanded disability status score showed strongest correlations in regions such as corpus callosum with qMRI metrics that are believed to be specific markers of axonal dysfunction, consistent with histologic data of others indicating axonal loss that is independent of focal lesions. Our results support that MS at least in part has a neurodegenerative component. [Copyright &y& Elsevier]

Abstract: In this work we provide an up-to-date short review of computational magnetic resonance imaging (MRI) and software tools that are widely used to process and analyze diffusion-weighted MRI data. A review of different methods used to acquire, model and analyze diffusion-weighted imaging data (DWI) is first provided with focus on diffusion tensor imaging (DTI). The major preprocessing, processing and post-processing procedures applied to DTI data are discussed. A list of freely available software packages to analyze diffusion MRI data is also provided. [Copyright &y& Elsevier]

Abstract: Recent studies demonstrated that diffusion tensor imaging (DTI) can provide information regarding white matter integrity of the corpus callosum (CC). In this study, DTI parameters were compared between cocaine dependent subjects (CDs) and non-drug using controls (NCs) in midsagittal CC. DTI images were acquired from 19 CDs and 18 age-matched NCs. The midsagittal CC was segmented into: genu, rostral body, anterior midbody, posterior midbody, isthmus, and splenium. Linear mixed models analyses showed that, relative to NCs, CDs had lower fractional anisotropy (FA), higher radial diffusivity (λ ⊥), and higher mean diffusivity (D av) in the isthmus; higher λ⊥ and D av in the rostral body; and lower FA in the splenium. After including mass of lifetime alcohol use in the mixed model analysis of covariance (ANCOVA) as a covariate, significant between group differences in λ ⊥ in the rostral body and isthmus remained. These results suggest that alterations in λ ⊥ in the rostral body and isthmus were mainly due to cocaine use, consistent with previous studies showing that cocaine may alter myelin integrity. Between group differences in FA in the isthmus and splenium, and D av in the rostral body and isthmus became non-significant after inclusion of alcohol use as a covariate. This is suggestive of alcohol influencing these values, or may be related to the decreased degrees of freedom for these effects. Consistent with clinical data of greater severity of drug use in smoked versus intranasal cocaine, subjects who smoked cocaine showed lower FA and higher λ ⊥ compared to intranasal CDs. [Copyright &y& Elsevier]

Abstract: The human brain uncinate fasciculus (UF) is an important cortico-cortical white matter pathway that directly connects the frontal and temporal lobes, although there is a lack of conclusive support for its exact functional role. Using diffusion tensor tractography, we extracted the UF, calculated its volume and normalized it with respect to each subject''s intracranial volume (ICV) and analyzed its corresponding DTI metrics bilaterally on a cohort of 108 right-handed children and adults aged 7–68 years. Results showed inverted U-shaped curves for fractional anisotropy (FA) with advancing age and U-shaped curves for radial and axial diffusivities reflecting white matter progressive and regressive myelination and coherence dynamics that continue into young adulthood. The mean FA values of the UF were significantly larger on the left side in children (p =0.05), adults (p =0.0012) and the entire sample (p =0.0002). The FA leftward asymmetry (Left>Right) is shown to be due to increased leftward asymmetry in the axial diffusivity (p <0.0001) and a lack of asymmetry (p >0.23) for the radial diffusivity. This is the first study to provide baseline normative macro and microstructural age trajectories of the human UF across the lifespan. Results of this study may lend themselves to better understanding of UF role in future behavioral and clinical studies. [Copyright &y& Elsevier]

Abstract: The mapping of the human brain white matter fiber networks relative to deep subcortical and cortical gray matter requires high spatial resolution which is challenged by the low signal-to-noise ratio. The purpose of this short report was to introduce a whole brain high spatial resolution diffusion tensor imaging (DTI) protocol that enabled for the first time the mapping of corticopontocerebellar, frontostriatal and thalamofrontal fiber pathways in addition to other limbic, commissural, association and projection white matter pathways relative to the segmented deep gray (e.g., caudate nuclei) and the cortical lobes. Our DTI acquisition protocol and analysis strategy provide important template for brain-behavior research and for teaching brain mapping and are clinically affordable for patient comfort. [Copyright &y& Elsevier]

Abstract: Several anatomical attributes of the human corpus callosum (CC) including the midsagittal cross-sectional area, thickness, and volume, have been used to assess CC integrity. We extended our previous lifespan quantitative diffusion tensor imaging (DTI) study of the regional CC midsagittal areas to include the CC volumes obtained from DTI fiber tracking. In addition to the entire CC tracked subvolumes we normalized volume with respect to each subject''s intracranial volume (ICV) and the corresponding DTI metrics of the different specialized fiber pathways of the CC on a cohort of 99 right-handed children and adults aged 7–59 years. Results indicated that the CC absolute volume, the normalized volume fraction, and the fractional anisotropy followed inverted U-shaped curves, while the radial diffusivities followed a U-shaped curve reflecting white matter progressive and regressive myelination dynamics that continue into young adulthood. Our study provides for the first time normative baseline macro- and microstructural age trajectories of the human CC subvolumes across the lifespan that can be helpful for normative behavioral and clinical studies. [Copyright &y& Elsevier]

Abstract: The midsagittal corpus callosum (CC) cross-sectional area subdivisions have been used as early and sensitive markers of human brain white matter connectivity, development, natural aging and disease. Despite the simplicity and conspicuity of the appearance of the CC on anatomical magnetic resonance imaging (MRI), the published quantitative MRI literature on its regional sex and age trajectories are contradictory. The availability of noninvasive quantitative methods to assess the CC regions across the human lifespan would help clarify its contribution to behavior and cognition. In this report, we extended the utility of a recently described semi-automated diffusion tensor imaging (DTI) tissue segmentation method to utilize the high orientation contrast of the CC on DTI. Using optimized DTI methods on a cohort of 121 right-handed children and adults aged 6–68 years, we examined the CC areas and corresponding DTI metrics of the different functionally specialized sectors of the CC. Both the area and fractional anisotropy metrics followed inverted U-shaped curves, while the mean and radial diffusivities followed U-curves reflecting white matter progressive and regressive myelination dynamics that continue into young adulthood. [Copyright &y& Elsevier]

Abstract: In this communication, a theoretical framework for quality control and parameter optimization in diffusion tensor imaging (DTI) is presented and validated. The approach is based on the analytical error propagation of the mean diffusivity (D av) obtained directly from the diffusion-weighted data acquired using rotationally invariant and uniformly distributed icosahedral encoding schemes. The error propagation of a recently described and validated cylindrical tensor model is further extrapolated to the spherical tensor case (diffusion anisotropy ∼0) to relate analytically the precision error in fractional tensor anisotropy (FA) with the mean diffusion-to-noise ratio (DNR). The approach provided simple analytical and empirical quality control measures for optimization of diffusion parameter space in an isotropic medium that can be tested using widely available water phantoms. [Copyright &y& Elsevier]

Abstract: Reduced fractional anisotropy (FA) in Diffusion Tensor Imaging (DTI) has been reported in cocaine dependent subjects compared to non-drug using controls. There are several pathological mechanisms that could be responsible for these findings, since FA can be reduced through damage to axonal tracts and by neuronal loss. One way of obtaining more information about pathology underlying changes in FA on DTI is diffusion tensor eigenvalues, representing diffusion along the fiber tract (λ 1) or perpendicular to the fiber tract (λ T). Thirteen cocaine dependent subjects and 18 healthy controls underwent full brain DTI. Eigenvalues λ 1 and λ T of the corpus callosum were compared between cocaine users and controls. For λ T there was a significant interaction of group×region of corpus callosum. Exploratory analysis of the subregions showed higher λ T in the genu of the anterior corpus callosum of cocaine dependent subjects compared to control subjects. For λ 1 there was no significant interaction of group×region of corpus callosum. Based on prior studies suggesting that alteration or damage to myelin increases diffusion perpendicular to the direction of fiber tracts (λ T) with minimal effect on λ 1 these findings are consistent with altered myelin in the corpus callosum in cocaine dependent subjects. [Copyright &y& Elsevier]

Background Neuroimaging machine learning studies have largely utilized supervised algorithms – meaning they require both neuroimaging scan data and corresponding target variables (e.g. healthy vs. diseased) to be successfully ‘trained’ for a prediction task. Noticeably, this approach may not be optimal or possible when the global structure of the data is not well known and the researcher does not have an a priori model to fit the data. New method We set out to investigate the utility of an unsupervised machine learning technique; t -distributed stochastic neighbour embedding ( t -SNE) in identifying ‘unseen’ sample population patterns that may exist in high-dimensional neuroimaging data. Multimodal neuroimaging scans from 92 healthy subjects were pre-processed using atlas-based methods, integrated and input into the t -SNE algorithm. Patterns and clusters discovered by the algorithm were visualized using a 2D scatter plot and further analyzed using the K -means clustering algorithm. Comparison with existing methods t -SNE was evaluated against classical principal component analysis. Conclusion Remarkably, based on unlabelled multimodal scan data, t -SNE separated study subjects into two very distinct clusters which corresponded to subjects’ gender labels (cluster silhouette index value = 0.79). The resulting clusters were used to develop an unsupervised minimum distance clustering model which identified 93.5% of subjects’ gender. Notably, from a neuropsychiatric perspective this method may allow discovery of data-driven disease phenotypes or sub-types of treatment responders. [ABSTRACT FROM AUTHOR]

Background: Anhedonia - a key symptom of depression - is highly associated with poorer outcomes and suicidal behavior. Alterations in the circuitry of reward-related brain regions have been robustly associated with anhedonia in unipolar depression, but not bipolar disorder (BD). We investigated white matter microstructures associated with anhedonia in participants with BD types I and II and first-degree relatives of patients with BD (BD-siblings).Methods: Eighty participants (BD types I and II: 56 [70%], and BD-siblings: 24 [30%]) underwent diffusion tensor imaging (DTI); Fractional anisotropy (FA) of different tracts were computed. Anhedonia was assessed using item 8, ("inability to feel'') of the MADRS scale. General linear models were used to compare the FA of different tracts in participants with and without anhedonia controlling for several clinical and demographic variables.Results: The mean age of the sample was 37 (± 11) years old, and 68.8% were female. Participants with anhedonia (32.5%) presented lower mean FA in the left uncinate fasciculus (UF) (p = 0.005), right temporal endings of the superior longitudinal fasciculus (SLFT) (p = 0.04), and in the left and right parietal endings of the superior longitudinal fasciculus (SLFP) (p = 0.003, and p = 0.04, respectively). Similar comparisons between participants with or without current depressive episodes and between participants with or without inner tension according to the MADRS did not show significant differences, specificity of the findings for anhedonia.Conclusions: Lower FA in the left UF and SLF are potential neuroimaging markers of anhedonia in individuals with BD and high-risk for BD. [ABSTRACT FROM AUTHOR]

Abstract: Analysis of crossing fibers is a challenging topic in recent diffusion-weighted imaging (DWI). Resolving crossing fibers is expected to bring major changes to present tractography results based on the standard tensor model. Model free approaches, like Q-ball or diffusion spectrum imaging, as well as multi-tensor models are used to unfold the different diffusion directions mixed in a voxel of DWI data. Due to its seeming simplicity, the two-tensor model (TTM) is applied frequently to provide two positive-definite tensors and the relative population fraction modeling two crossing fiber branches. However, problems with uniqueness and noise instability are apparent. To stabilize the fit, several of the 13 physical parameters are fixed ad hoc, before fitting the model to the data. Our analysis of the TTM aims at fitting procedures where ad hoc parameters are avoided. Revealing sources of instability, we show that the model''s inherent ambiguity can be reduced to one scalar parameter which only influences the fraction and the eigenvalues of the TTM, whereas the diffusion directions are not affected. Based on this, two fitting strategies are proposed: the parsimonious strategy detects the main diffusion directions without extra parameter fixation, to determine the eigenvalues and the population fraction an empirically motivated condition must be added. The expensive strategy determines all 13 physical parameters of the TTM by a fit to DWIs alone; no additional assumption is necessary. Ill-posedness of the model in case of noisy data is cured by denoising of the data and by L-curve regularization combined with global minimization performing a least-squares fit of the full model. By model simulations and real data applications, we demonstrate the feasibility of our fitting strategies and achieve convincing results. Using clinically affordable diffusion acquisition paradigms (encoding numbers: 21, 2*15, 2*21) and b values (b =500–1500s/mm2), this methodology can place the TTM parameters involved in crossing fibers on a more empirical basis than fitting procedures with technical assumptions. [Copyright &y& Elsevier]

Abstract: In this work, we present a framework to fuse and quantify tissue microstructural attributes (e.g. diffusion, functional, relaxation and perfusion MRI) using high spatial resolution T1-weighted volumetric measurements. The proposed computational procedures can be implemented by utilizing advanced, image segmentation, registration and diffusion tensor image processing software. Feasibility of the framework is also demonstrated using in-house developed software and freely available software such as FreeSurfer for regional tissue segmentation, Advanced Normalization Tools (ANTs) for registration and DTIStudio for fiber tracking and diffusion tensor data processing. We also demonstrate the application of these methods in the provision of quality control measures to assess the fidelity of tissue segmentation and multi-modal MRI registration. [Copyright &y& Elsevier]

Abstract: Mapping the human brain frontostriatal pathways using noninvasive diffusion tensor imaging (DTI) has been hampered by the inadequate imaging sensitivity, poor spatial resolution, lower tensor anisotropy within gray matter, increased partial volume averaging effects and poor signal-to-noise ratio. We investigated for the first time the utility of high spatial resolution DTI-based fiber-tractography using the fiber assignment by continuous tracking (FACT) to reconstruct and quantify bilaterally the prefronto-caudo-thalamic connections within the human brain at 3T. Five healthy right-handed men (age range 24–37 years) were studied. We traced the anterior thalamic radiation and prefronto-caudo-thalamic pathways bilaterally and measured the volume of each tract and the corresponding diffusion tensor metrics in all subjects. The anterior thalamic radiation tract volume and corresponding fractional anisotropy (FA) were significantly larger bilaterally than prefronto-caudate pathway, whereas the mean diffusivity (D av) values were similar (p >0.7). For both anterior thalamic radiation and prefronto-caudate pathway the tract volume and corresponding DTI metrics (FA, D av) were not significantly different between the two hemispheres (p >0.2). Our DTI acquisition protocol and analysis permitted the reconstruction of the connectivity of the caudate with the thalamus as well as with the prefrontal cortex and allowed tracking of the whole trajectory of the prefronto-caudo-thalamic pathway. [ABSTRACT FROM AUTHOR]

• First time tracing of the dorsal thalamohypothalamic tract (DTH) and detailed anatomy. • Review of possible functions of the dorsal thalamo-hypothalamic connectivity. • Revealing the proximity of the forniceal structures running side by side with the DTH. As a non-limbic structure, the human thalamus is the most important modulator of the limbic system. The hypothalamus plays vital roles in the survival of species by regulating fear, learning, feeding behavior, circadian rhythm, sociosexual and reproductive activities of the limbic system through connections with the thalamus. The detailed anatomy of the pathways responsible for mediating these responses, however, is yet to be determined. The mammillothalamic tract is known as the major direct thalamo-hypothalamic connection in the primates including the human brain connecting the ventral thalamus to the dorsal hypothalamus. Multiple dissection animal studies revealed additional connections specially from the dorsal thalamus to the ventral hypothalamic nuclei. Diffusion weighted imaging may be helpful in better visualizing the surgical anatomy of this additional connectivity noninvasively. This study aimed to investigate the utility of high spatial and high angular resolution diffusion weighted tractography technique for mapping the trajectory of this dorsal thalamic connectivity with the ventral hypothalamus in the human brain. We studied 30 healthy human subjects. Using a high-resolution diffusion weighted tractography technique, for the first time, we were able to delineate and reconstruct the trajectory of the dorsal thalamo-hypothalamic tract (DTH). We further revealed the close relationship of the DTH, fornix and hippocampus in healthy adult human brain. [ABSTRACT FROM AUTHOR]

The cerebellum is shown to be involved in some limbic functions of the human brain such as emotion and affect. The major connection of the cerebellum with the limbic system is known to be through the cerebello-hypothalamic pathways. The consensus is that the projections from the cerebellar nuclei to the limbic system, and particularly the hypothalamus, or from the hypothalamus to the cerebellar nuclei, are through multisynaptic pathways in the bulbar reticular formation. The detailed anatomy of the pathways responsible for mediating these responses, however, is yet to be determined. Diffusion tensor imaging may be helpful in better visualizing the surgical anatomy of the cerebello-ponto-hypothalamic (CPH) pathway. This study aimed to investigate the utility of high-spatial-resolution diffusion tensor tractography for mapping the trajectory of the CPH tract in the human brain. Fifteen healthy adults were studied. We delineated, for the first time, the detailed trajectory of the CPH tract of the human brain in fifteen normal adult subjects using high-spatial-resolution diffusion tensor tractography. We further revealed the close relationship of the CPH tract with the optic tract, temporo-pontine tract, amygdalofugal tract and the fornix in the human brain. [ABSTRACT FROM AUTHOR]

Previous studies have reported abnormalities of white-matter diffusivity in pediatric bipolar disorder. However, it has not been established whether these abnormalities are able to distinguish individual subjects with pediatric bipolar disorder from healthy controls with a high specificity and sensitivity. Diffusion-weighted imaging scans were acquired from 16 youths diagnosed with DSM-IV bipolar disorder and 16 demographically matched healthy controls. Regional white matter tissue microstructural measurements such as fractional anisotropy, axial diffusivity and radial diffusivity were computed using an atlas-based approach. These measurements were used to ‘train’ a support vector machine (SVM) algorithm to predict new or ‘unseen’ subjects’ diagnostic labels. The SVM algorithm predicted individual subjects with specificity=87.5%, sensitivity=68.75%, accuracy=78.12%, positive predictive value=84.62%, negative predictive value=73.68%, area under receiver operating characteristic curve (AUROC)=0.7812 and chi-square p -value=0.0012. A pattern of reduced regional white matter fractional anisotropy was observed in pediatric bipolar disorder patients. These results suggest that atlas-based diffusion weighted imaging measurements can distinguish individual pediatric bipolar disorder patients from healthy controls. Notably, from a clinical perspective these findings will contribute to the pathophysiological understanding of pediatric bipolar disorder. [ABSTRACT FROM AUTHOR]

The human limbic system is composed of gray and white matter structures which have been known to have a role in core processes such as motivation, memory, emotion, social behavior, self-awareness as well as certain primitive instincts. Multiple functional studies investigated some of these brain tasks in human brain limbic system. However, the underlying fine fiber pathways of the limbic system including the trajectory of the stria terminalis have not been delineated separately by prior diffusion weighted imaging. The ability to trace the underlying fiber anatomy noninvasively using diffusion tensor tractography (DTT) would be helpful to study the neurophysiology of these tracts in different functions in future functional studies. Few studies have focused on the stria terminalis using diffusion tensor tractography. Yet, the trajectory of the stria terminalis and some fine subtrajectories of the fornix have not been elucidated by prior DTT studies. We decided to further investigate these fine neuronal trajectory using tractography and high spatial resolution diffusion tensor imaging on 3T. Fifteen healthy right-handed men (age range 24–37 years) were studied. We delineated the detailed trajectories of the stria terminalis and fornix bilaterally in fifteen normal adult human brains. Using a high resolution DTT technique, we demonstrate for the first time, the trajectory of stria terminalis as well as detailed precommissural and postcommissural connectivity of the forniceal columns. [ABSTRACT FROM AUTHOR]

Introduction Despite a wide variety of therapeutic interventions for major depressive disorder (MDD), treatment resistant depression (TRD) remains to be prevalent and troublesome in clinical practice. In recent years, deep brain stimulation (DBS) has emerged as an alternative for individuals suffering from TRD not responding to combining antidepressants, multiple adjunctive strategies and electroconvulsive therapy (ECT). Although the best site for TRD-DBS is still unclear, pilot data suggests that the medial forebrain bundle (MFB) might be a key target to accomplish therapeutic efficacy in TRD patients. Objective To explore the anatomic, electrophysiologic, neurocognitive and treatment data supporting the MFB as a target for TRD-DBS. Results The MFB connects multiple targets involved in motivated behavior, mood regulation and antidepressant response. Specific phenomenology associated with TRD can be linked specifically to the superolateral branch (sl) of the MFB (slMFB). TRD patients who received DBS-slMFB reported high response/remission rates with an improvement in functioning and no significant adverse outcomes in their physical health or neurocognitive performance. Discussion The slMFB is an essential component of a network of structural and functional pathways connecting different areas possibly involved in the pathogenesis of mood disorders. Therefore, the slMFB should be considered as an exciting therapeutic target for DBS therapy to achieve a sustained relief in TRD patients. Conclusion There is an urgent need for clinical trials exploring DBS-slMFB in TRD. Further efforts should pursue measuring baseline pro-inflammatory cytokines, oxidative stress, and cognition as possible biomarkers of DBS-slMFB response in order to aid clinicians in better patient selection. [ABSTRACT FROM AUTHOR]

Abstract: Diffusion tensor (DT) imaging measures the random molecular diffusion of water in vivo and provides information on the microstructure of tissue. Ischemic brain damage leads to tissue disorganization and structural lost. We aimed to evaluate these changes in a rat model of focal stroke from the hyperacute to chronic phase by utilizing several DT indices. Adult male Wistar rats, subjected to temporary focal cerebral ischemia by suture occlusion of the middle cerebral artery for 90min, and sham controls were serially imaged at 4.7Tesla. DT scans were collected repeatedly during the hyperacute (2 and 3.5h), acute (1, 2, and 3days), subacute (4, 7, and 14days), and chronic (4, 6, and 8weeks) phases. We measured the evolution of DT indices (mean diffusivity (MD), axial diffusivity (λ║), radial diffusivity (λ┴), and fractional anisotropy (FA)) in the cortex, subcortex, and corpus callosum of the ischemic hemisphere. In the hyperacute phase, MD, λ║, and λ┴ reduced with no change in FA. From the acute to subacute phase, MD, λ║, and λ┴ normalized and thereafter increased, whereas FA decreased in all the tissues. In the chronic phase, MD, λ║, and λ┴ continued to rise, whereas FA normalized in the corpus callosum and subcortex, but remained low in the cortex. We described structural tissue changes in ischemic rat brain longitudinally utilizing DT analysis. DT indices reveal different individual patterns reflecting different facades and phases of tissue injury. The use of several DT indices may improve accuracy in estimating the age of the brain injury and in detecting ongoing pathological events. [Copyright &y& Elsevier]

Cocaine use continues to be a significant public health problem with limited treatment options and no approved pharmacotherapies. Cognitive-behavioral therapy (CBT) remains the mainstay treatment for preventing relapse, however, people with chronic cocaine use display cognitive impairments that are associated with poor response to CBT. Emerging evidence in animal and human studies suggests that the peroxisome proliferator-activated receptor-gamma (PPAR- γ) agonist, pioglitazone, improves white matter integrity that is essential for cognitive function. This project will determine whether adjunctive use of pioglitazone enhances the effect of CBT in preventing relapse during the early phase of recovery from cocaine use disorder. This paper describes the design of a mechanism-focused phase 2 randomized clinical trial that aims first to evaluate the effects of pioglitazone on targeted mechanisms related to white matter integrity, cognitive function, and cocaine craving; and second, to evaluate the extent to which improvements on target mechanisms predict CBT response. Positive results will support pioglitazone as a potential cognitive enhancing agent to advance to later stage medication development research. [ABSTRACT FROM AUTHOR]

• First time diffusion weighted tractography of the parieto-occipito-hypothalamic tract (POHT) and detailed anatomy. • Revealing the posterior cortico-limbic circuits. • Revealing major adjacent fiber tracts including the inferior fronto-occipital fasciculus (IFOF) and amygdalofugal tract running side by side with the POHT. The human hypothalamus is at the center of the human limbic system anatomically and physiologically. The hypothalamus plays pivotal roles in controlling autonomic responses and instinctive behaviors such as regulating fear, aggression, learning, feeding behavior, circadian rhythm, and reproductive activities. The detailed anatomy of the pathways responsible for mediating these responses, however, is yet to be determined. The inhibitory effect of the cerebral cortex on the hypothalamus in many autonomic responses, suggests the presence of direct connection between the cortex and hypothalamic nuclei. While, there is ample information to support the cortico-hypothalamic association between the prefrontal cortex and hypothalamic nuclei, the information regarding a direct posterior cortico-hypothalamic alliance is scant. The visuosensory information may be crucial for the limbic system to regulate some of the important limbic functions. Multiple dissection animal studies revealed direct posterior cortical connectivity with the hypothalamic nuclei. However, a direct cortico-hypothalamic connectivity from the parieto-occipital cortices has not been revealed in the human brain yet. Diffusion weighted imaging (DWI) may be helpful in better visualizing the anatomy of this direct posterior cortico-limbic connectivity noninvasively in the human brain. We studied 30 healthy human subjects. Using a high-spatial and high angular resolution diffusion weighted tractography technique, for the first time, we were able to delineate and reconstruct the trajectory of the parieto-occipito-hypothalamic tract. [ABSTRACT FROM AUTHOR]