Dynamic Imaging of Blood Coagulation Within the Hematoma of Patients With Acute Hemorrhagic Stroke.

BACKGROUND: The dynamics of blood clot (combination of Hb [hemoglobin], fibrin, and a higher concentration of aggregated red blood cells) formation within the hematoma of an intracerebral hemorrhage is not well understood. A quantitative neuroimaging method of localized coagulated blood volume/distribution within the hematoma might improve clinical decision-making. METHODS: The deoxyhemoglobin of aggregated red blood cells within extravasated blood exhibits a higher magnetic susceptibility due to unpaired heme iron electrons. We propose that coagulated blood, with higher aggregated red blood cell content, will exhibit (1) a higher positive susceptibility than noncoagulated blood and (2) increase in fibrin polymerization-restricted localized diffusion, which can be measured noninvasively using quantitative susceptibility mapping and diffusion tensor imaging. In this serial magnetic resonance imaging study, we enrolled 24 patients with acute intracerebral hemorrhage between October 2021 to May 2022 at a stroke center. Patients were 30 to 70 years of age and had a hematoma volume >15 cm3 and National Institutes of Health Stroke Scale score >1. The patients underwent imaging 3×: within 12 to 24 (T1), 36 to 48 (T2), and 60 to 72 (T3) hours of last seen well on a 3T magnetic resonance imaging system. Three-dimensional anatomic, multigradient echo and 2-dimensional diffusion tensor images were obtained. Hematoma and edema volumes were calculated, and the distribution of coagulation was measured by dynamic changes in the susceptibilities and fractional anisotropy within the hematoma. RESULTS: Using a coagulated blood phantom, we demonstrated a linear relationship between the percentage coagulation and susceptibility (R2=0.91) with a positive red blood cell stain of the clot. The quantitative susceptibility maps showed a significant increase in hematoma susceptibility (T1, 0.29±0.04 parts per millions; T2, 0.36±0.04 parts per millions; T3, 0.45±0.04 parts per millions; P<0.0001). A concomitant increase in fractional anisotropy was also observed with time (T1, 0.40±0.02; T2, 0.45±0.02; T3, 0.47±0.02; P<0.05). CONCLUSIONS: This quantitative neuroimaging study of coagulation within the hematoma has the potential to improve patient management, such as safe resumption of anticoagulants, the need for reversal agents, the administration of alteplase to resolve the clot, and the need for surgery.

Identifying the white matter pathways involved in multiple sclerosis-related tremor using diffusion tensor imaging.

Background: Tremor affects up to 45% of patients with Multiple Sclerosis (PwMS). Current understanding is based on insights from other neurological disorders, thus, not fully addressing the distinctive aspects of MS pathology. Objective: To characterize the brain white matter (WM) correlates of MS-related tremor using diffusion tensor imaging (DTI). Methods: In a prospective case-control study, PwMS with tremor were assessed for tremor severity and underwent MRI scans including DTI. PwMS without tremor served as matched controls. After tract selection and segmentation, the resulting diffusivity measures were used to calculate group differences and correlations with tremor severity. Results: This study included 72 PwMS. The tremor group (n = 36) exhibited significant changes in several pathways, notably in the right inferior longitudinal fasciculus (Cohen's d = 1.53, q < 0.001) and left corticospinal tract (d = 1.32, q < 0.001), compared to controls (n = 36). Furthermore, specific tracts showed a significant correlation with tremor severity, notably in the left medial lemniscus (Spearman's coefficient [rsp] = -0.56, p < 0.001), and forceps minor of corpus callosum (rsp = -0.45, p < 0.01). Conclusion: MS-related tremor is associated with widespread diffusivity changes in WM pathways and its severity correlates with commissural and sensory projection pathways, which suggests a role for proprioception or involvement of the dentato-rubro-olivary circuit.

Unfolding the direct connectivity of the occipital cortex with the hypothalamic, septal and BNST nuclei of the human brain.

The hypothalamus plays essential roles in the human brain by regulating feeding, fear, aggression, reproductive behaviors, and autonomic activities. The septal nuclei and the bed nucleus of stria terminalis (BNST) are also known to be involved in control of autonomic, motivational, learning, emotional and associative processes in the human brain. Multiple animal dissection studies have revealed direct connectivity between central limbic gray matter nuclei and occipital cortex, particularly from the hypothalamic, septal and BNST nuclei. However, the detailed anatomy of this connectivity in the human brain has yet to be determined. The primary objective of this study was to explore the utility of high spatial and high angular resolution diffusion weighted tractography techniques for mapping the connectivity pathways between the occipital cortex and central limbic gray matter nuclei in the human brain. We studied 30 healthy adult human brains, delineated, and reconstructed the trajectory of the occipito-hypothalamic/septal/BNST for the first time in the human brain.

Longitudinal Morphometric Changes in the Corticospinal Tract Shape After Hemorrhagic Stroke.

Deep intracerebral hemorrhage (ICH) exerts a direct force on corticospinal tracts (CST) causing shape deformation. Using serial MRI, Generalized Procrustes Analysis (GPA), and Principal Components Analysis (PCA), we temporally evaluated the change in CST shape. Thirty-five deep ICH patients with ipsilesional-CST deformation were serially imaged on a 3T-MRI with a median imaging time of day-2 and 84 of onset. Anatomical and diffusion tensor images (DTI) were acquired. Using DTI color-coded maps, 15 landmarks were drawn on each CST and the centroids were computed in 3 dimensions. The contralesional-CST landmarks were used as a reference. The GPA outlined the shape coordinates and we superimposed the ipsilesional-CST shape at the two-time points. A multivariate PCA was applied to identify eigenvectors associated with the highest percentile of change. The first three principal components representing CST deformation along the left-right (PC1), anterior-posterior (PC2), and superior-inferior (PC3) respectively were responsible for 57.9% of shape variance. The PC1 (36.1%, p < 0.0001) and PC3 (9.58%, p < 0.01) showed a significant deformation between the two-time points. Compared to the contralesional-CST, the ipsilesional PC scores were significantly (p < 0.0001) different only at the first-timepoint. A significant positive association between the ipsilesional-CST deformation and hematoma volume was observed. We present a novel method to quantify CST deformation caused by ICH. Deformation most often occurs in left-right axis (PC1) and superior-inferior (PC3) directions. As compared to the reference, the significant temporal difference at the first time point suggests CST restoration over time.

Functional assessment of the dural lymphatic vessels using dynamic contrast MRI in multiple sclerosis.

BACKGROUND AND PURPOSE: The discovery of glymphatic function in the human brain has generated interest in waste clearance mechanisms in neurological disorders such as multiple sclerosis (MS). However, noninvasive in vivo functional assessment is currently lacking. This work studies the feasibility of a novel intravenous dynamic contrast MRI method to assess the dural lymphatics, a purported pathway contributing to glymphatic clearance. METHODS: This prospective study included 20 patients with MS (17 women; age = 46.4 [27, 65] years; disease duration = 13.6 [2.1, 38.0] years, expanded disability status score (EDSS) = 2.0 [0, 6.5]). Patients were scanned on a 3.0T MRI system using intravenous contrast-enhanced fluid-attenuated inversion recovery MRI. Signal in the dural lymphatic vessel along the superior sagittal sinus was measured to calculate peak enhancement, time to maximum enhancement, wash-in and washout slopes, and the area under the time-intensity curve (AUC). Correlation analysis was performed to examine the relationship between the lymphatic dynamic parameters and the demographic and clinical characteristics, including the lesion load and the brain parenchymal fraction (BPF). RESULTS: Contrast enhancement was detected in the dural lymphatics in most patients 2-3 min after contrast administration. BPF had a significant correlation with AUC (p < .03), peak enhancement (p < .01), and wash-in slope (p = .01). Lymphatic dynamic parameters did not correlate with age, BMI, disease duration, EDSS, or lesion load. Moderate trends were observed for correlation between patient age and AUC (p = .062), BMI and peak enhancement (p = .059), and BMI and AUC (p = .093). CONCLUSION: Intravenous dynamic contrast MRI of the dural lymphatics is feasible and may be useful in characterizing its hydrodynamics in neurological diseases.

The Cortico-Limbo-Thalamo-Cortical Circuits: An Update to the Original Papez Circuit of the Human Limbic System.

The Papez circuit, first proposed by James Papez in 1937, is a circuit believed to control memory and emotions, composed of the cingulate cortex, entorhinal cortex, parahippocampal gyrus, hippocampus, hypothalamus, and thalamus. Pursuant to James Papez, Paul Yakovlev and Paul MacLean incorporated the prefrontal/orbitofrontal cortex, septum, amygdalae, and anterior temporal lobes into the limbic system. Over the past few years, diffusion-weighted tractography techniques revealed additional limbic fiber connectivity, which incorporates multiple circuits to the already known complex limbic network. In the current review, we aimed to comprehensively summarize the anatomy of the limbic system and elaborate on the anatomical connectivity of the limbic circuits based on the published literature as an update to the original Papez circuit.

Disruption of specific white matter tracts is associated with neurogenic lower urinary tract dysfunction in women with multiple sclerosis.

OBJECTIVE: To identify specific white matter tracts (WMTs) whose disruption is associated with the severity of neurogenic lower urinary tract dysfunction (NLUTD) in two independent cohorts of women with multiple sclerosis (MS) and NLUTD. METHODS: Cohort 1 consisted of twenty-eight women with MS and NLUTD. The validation cohort consisted of 10 women with MS and NLUTD. Eleven healthy women served as controls. Participants of both MS cohorts had the same inclusion and exclusion criteria. Both MS cohorts and the healthy controls underwent the same clinical assessment and functional MRI (fMRI) protocol, except that the validation MS cohort underwent 7-Tesla fMRI scan. Fifteen WMTs (six coursing to relevant brainstem areas) involved in bladder control were a priori regions of interest (ROI). Spearman's correlation test was performed between each the Fractional Anisotropy (FA) and mean diffusivity (MD) of each WMT and the clinical parameters. RESULTS: Overall, we found a very high degree of overlap (100% of a priori ROI) in the tracts identified by our correlation analysis as having the greatest contribution to NLUTD symptoms in MS women. The right inferior cerebellar peduncle, left posterior limb of internal capsule, and left superior cerebellar peduncle displayed significant associations to the greatest number of clinical parameters. CONCLUSIONS: Our correlation analysis supports the role of specific WMT disruptions in the contribution of symptoms in women with MS and NLUTD, as confirmed in two independent MS cohorts.

Cerebrovascular Effects of Lower Body Negative Pressure at 3T MRI: Implications for Long-Duration Space Travel.

BACKGROUND: Optic disc edema develops in most astronauts during long-duration spaceflight. It is hypothesized to result from weightlessness-induced venous congestion of the head and neck and is an unresolved health risk of space travel. PURPOSE: Determine if short-term application of lower body negative pressure (LBNP) could reduce internal jugular vein (IJV) expansion associated with the supine posture without negatively impacting cerebral perfusion or causing IJV flow stasis. STUDY TYPE: Prospective. SUBJECTS: Nine healthy volunteers (six women). FIELD STRENGTH/SEQUENCE: 3T/cine two-dimensional phase-contrast gradient echo; pseudo-continuous arterial spin labeling single-shot gradient echo echo-planar. ASSESSMENT: The study was performed with two sequential conditions in randomized order: supine posture and supine posture with 25 mmHg LBNP (LBNP25 ). LBNP was achieved by enclosing the lower extremities in a semi-airtight acrylic chamber connected to a vacuum. Heart rate, bulk cerebrovasculature flow, IJV cross-sectional area, fractional IJV outflow relative to arterial inflow, and cerebral perfusion were assessed in each condition. STATISTICAL TESTS: Paired t-tests were used to compare measurement means across conditions. Significance was defined as P < 0.05. RESULTS: LBNP25 significantly increased heart rate from 64 ± 9 to 71 ± 8 beats per minute and significantly decreased IJV cross-sectional area, IJV outflow fraction, cerebral arterial flow rate, and cerebral arterial stroke volume from 1.28 ± 0.64 to 0.56 ± 0.31 cm2 , 0.75 ± 0.20 to 0.66 ± 0.28, 780 ± 154 to 708 ± 137 mL/min and 12.2 ± 2.8 to 9.7 ± 1.7 mL/cycle, respectively. During LBNP25 , there was no significant change in gray or white matter cerebral perfusion (P = 0.26 and P = 0.24 respectively) and IJV absolute mean peak flow velocity remained ≥4 cm/sec in all subjects. DATA CONCLUSION: Short-term application of LBNP25 reduced IJV expansion without decreasing cerebral perfusion or inducing IJV flow stasis. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 1.

Characterizing the time course of cerebrovascular reactivity in multiple sclerosis.

BACKGROUND AND PURPOSE: Changes in cerebral perfusion occur early in relapsing and progressive multiple sclerosis (MS) patients, though whether cerebral blood flow (CBF) can be altered by therapy is unknown. We sought to characterize the time course of change in CBF (cerebral vascular reactivity [CVR]), following intravenous (IV) acetazolamide (ACZ) in whole brain and within various gray and white matter brain regions in MS patients. METHODS: We enrolled five relapsing MS patients on injectable therapies. Participants received a 1000 mg IV bolus of ACZ and CBF was measured using pseudocontinuous arterial spin labeling MRI. To quantify differences in time course between patients, we calculated the numerical integration of CVR over time using the trapezoidal rule to estimate area under the curve (AUC(CVR) ). RESULTS: A change in whole brain CBF of 30%-65% was seen in all participants at 15 minutes after ACZ challenge. CBF increases >20% above baseline were sustained for 90 minutes within whole-brain, normal-appearing white matter and total T2-hyperintense lesioned tissue. AUC(CVR) values for both gray (cortical and deep gray matter) and white (normal-appearing and T2-lesioned) matter regions were similar between patients. CONCLUSION: Our findings show a prolonged time course in vascular reactivity after ACZ stimulus in MS patients with a similar time course for both gray and white matter brain regions, including in previously injured tissue. Our preliminary results suggest that blood flow can be augmented in the established MS lesion suggesting that even previously injured tissue might be responsive to treatment.

Investigation of endophenotype potential of decreased fractional anisotropy in pediatric bipolar disorder patients and unrelated offspring of bipolar disorder patients.

BACKGROUND: Bipolar disorder (BD) is a severe psychiatric disorder associated with structural and functional brain abnormalities, some of which have been found in unaffected relatives as well. In this study, we examined the potential role of decreased fractional anisotropy (FA) as a BD endophenotype, in adolescents at high risk for BD. METHODS: We included 15 offspring of patients with BD, 16 pediatric BD patients, and 16 matched controls. Diffusion weighted scans were obtained on a 3T scanner using an echo-planar sequence. Scans were segmented using FreeSurfer. RESULTS: Our results showed significantly decreased FA in six brain areas of offspring group; left superior temporal gyrus (LSTG; P < .0001), left transverse temporal gyrus (LTTG; P = .002), left banks of the superior temporal sulcus (LBSTS; P = .002), left anterior cingulum (LAC; P = .003), right temporal pole (RTP; P = .004) and left frontal pole (LFP; P = .017). On analysis, LSTG, LAC, and RTP demonstrated a potential to be an endophenotype when comparing all three groups. FA values in three regions, LBSTS, LTTG, and LFP were increased only in controls. CONCLUSION: Our findings point at decreased FA as a possible endophenotype for BD, as they were found in children of patients with BD. Most of these areas were previously found to have morphological and functional changes in adult and pediatric BD, and are thought to play important roles in affected domains of functioning. Prospective follow up studies should be performed to detect reliability of decreased FA as an endophenotype and effects of treatment on FA.

White matter microstructure associated with anhedonia among individuals with bipolar disorders and high-risk for bipolar disorders.

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.

Targeting white matter neuroprotection as a relapse prevention strategy for treatment of cocaine use disorder: Design of a mechanism-focused randomized clinical trial.

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.

Diffusion Tensor Imaging Correlates of Concussion Related Cognitive Impairment.

Introduction: Cognitive impairment after concussion has been widely reported, but there is no reliable imaging biomarker that predicts the severity of cognitive decline post-concussion. This study tests the hypothesis that patients with a history of concussion and persistent cognitive impairment have fractional anisotropy (FA) and mean diffusivity (MD) values from diffusion tensor imaging (DTI) that are specifically associated with poor performance on the Montreal Cognitive Assessment (MoCA). Methods: Fifty-three subjects (19 females) with concussions and persistent cognitive symptoms had MR imaging and the MoCA. Imaging was analyzed by atlas-based, whole-brain DTI segmentation and FLAIR lesion segmentation. Then, we conducted a random forest-based recursive feature elimination (RFE) with 10-fold cross-validation on the entire dataset, and with partial correlation adjustment for age and lesion load. Results: RFE showed that 11 DTI variables were found to be important predictors of MoCA scores. Partial correlation analyses, corrected for age and lesion load, showed significant correlations between MoCA scores and right fronto-temporal regions: inferior temporal gyrus MD (r = -0.62, p = 0.00001), middle temporal gyrus MD (r = -0.54, p = 0.0001), angular gyrus MD (r = -0.48, p = 0.0008), and inferior frontal gyrus FA (r = 0.44, p = 0.002). Discussion: This is the first study to demonstrate a correlation between MoCA scores and DTI variables in patients with a history of concussion and persistent cognitive impairment. This kind of research will significantly increase our understanding of why certain persons have persistent cognitive changes after concussion which, in turn, may allow us to predict persistent impairment after concussion and suggest new interventions.

Association of Structural Changes in the Brain and Retina After Long-Duration Spaceflight.

IMPORTANCE: Long-duration spaceflight induces structural changes in the brain and eye. Identification of an association between cerebral and ocular changes could help determine if there are common or independent causes and inform targeted prevention strategies or treatments. OBJECTIVE: To determine if there is an association between quantitative changes in intracranial compartment volumes and peripapillary total retinal thickness after spaceflight. DESIGN, SETTING, AND PARTICIPANTS: This cohort study included healthy International Space Station crew members before and immediately after long-duration spaceflight. Data on race were not collected. Analysis was conducted from September to November 2020. EXPOSURES: Long-duration spaceflight (mean [SD], 191 [55] days). MAIN OUTCOMES AND MEASURES: Optical coherence tomography-derived peripapillary total retinal thickness as a quantitative assessment and early sign of optic disc edema and magnetic resonance imaging-derived measures of lateral ventricle volume, white matter volume, and whole brain plus cerebrospinal fluid volume. RESULTS: In 19 healthy crew members included in this study (5 women [26.3%], 14 men [73.7%]; mean [SD] age, 45.2 [6.4] years), analyses revealed a positive, although not definitive, association between spaceflight-induced changes in total retinal thickness and lateral ventricle volume (4.7-µm increase in postflight total retinal thickness [95% CI, -1.5 to 10.8 µm; P = .13] per 1-mL postflight increase in lateral ventricle volume). Adjustments for mission duration improved the strength of association (5.1 µm; 95% CI, -0.4 to 10.5 µm; P = .07). No associations were detected between spaceflight-induced changes in total retinal thickness and white matter volume (0.02 µm; 95% CI, -0.5 to 0.5 µm; P = .94) or brain tissue plus cerebrospinal fluid volume, an estimate of intracranial volume (0.02 µm; 95% CI, -0.6 to 0.6 µm; P = .95). CONCLUSIONS AND RELEVANCE: These results help characterize spaceflight-associated neuro-ocular syndrome and the physiologic associations of headward fluid shifts with outcomes during spaceflight on the central nervous system. The possibly weak association between increased total retinal thickness and lateral ventricle volume suggest that while weightlessness-induced fluid redistribution during spaceflight may be a common stressor to the brain and retina, the development of optic disc edema appears to be uncoupled with changes occurring in the intracranial compartment.

Overview of Diffusion Tensor, Diffusion Kurtosis, and Q-space Imaging and Software Tools.

This work offers a short up-to-date review of diffusion-weighted MR imaging (dMRI) and software tools that are used widely to process and analyze clinical dMRI. A consolidated dMRI protocol for clinical applications that enables the mapping of tissue microstructural attributes is presented.

Longitudinal neuroimaging evaluation of the corticospinal tract in patients with stroke treated with autologous bone marrow cells.

Bone marrow mononuclear cells (MNCs) attenuate secondary degeneration and enhance recovery in stroke animal models. In a nonrandomized clinical trial, we imaged 37 patients with stroke: 17 patients treated with MNCs (treated) and 20 patients who received standard of care (nontreated) at 1, 3, and 12 months onset of stroke on 3.0T MRI system. Three-dimensional anatomical and diffusion tensor images were obtained. The integrity of the corticospinal tract was assessed by measuring absolute and relative fractional anisotropy (FA) and mean diffusivity (MD) in the rostral pons (RP), posterior limb of the internal capsule, and corona radiata by drawing regions of interest. Infarct volume and stroke severity, which was assessed via the NIH Stroke Scale (NIHSS), were higher in the MNC group compared with the nontreated patients, which is a major limitation. Overall, the relative FA (rFA) of the nontreated patients exhibited continued reduction and an increase in relative MD (rMD) from 1 to 12 months, whereas despite larger infarcts and higher severity, treated patients displayed an increase in rFA from 3 to 12 months and no change in rMD. Contrary to the nontreated group, the treated patients' rFA was also significantly correlated (P < .05) with NIHSS score in the RP at all time points, whereas rMD at the last two.

A meta-analysis of tract-based spatial statistics studies examining white matter integrity in cocaine use disorder.

Tract-based spatial statistics (TBSS) of diffusion tensor imaging (DTI) studies have consistently shown diminished white matter (WM) integrity for individuals with cocaine use disorder (CUD). The present study used seed-based d mapping (SDM) to determine the extent to which a systematic difference in the WM integrity of cocaine users may exist (as compared with that of healthy controls). Articles from 2006 (when TBSS was first developed) to present were reviewed, with eight selected for inclusion. Meta-analysis found lower fractional anisotropy (FA) in the genu of the corpus callosum for cocaine users, with a small-to-moderate peak effect size (Hedge's g = -0.331). Sensitivity analyses mostly supported the robustness of the obtained difference. Differences detected at exploratory thresholds for significance suggested insult to WM integrity extending beyond the corpus callosum. The present results compliment a previous region-of-interest (ROI)-based meta-analysis of DTI studies in individuals with CUD. These findings have significant implications for the potential role of neuroprotective agents in the treatment of CUD and merit additional iteration as more studies accrue in the literature.

Frontal aslant tracts as correlates of lexical retrieval in MS.

INTRODUCTION: Previous studies reveal that a newly described white matter pathway, the frontal aslant tract (FAT), connecting inferior and superior frontal gyri has a role in speech and language functions. We explored the role of this tract in a phonemic and semantic fluency tasks in a cohort of multiple sclerosis patients diagnosed with cognitive impairment. METHODS: Thirty-five MS patients with varying degrees of cognitive impairment underwent diffusion tensor imaging and the Controlled Associated Word Test. Fractional anisotropy (FA) of FAT and arcuate fasciculus (AF) were obtained through a supervised, atlas-based tissue segmentation and parcellation method. Phonemic and semantic fluency scores were obtained from COWAT. We ran a multivariate regression model, and partial correlation analyses adjusted for age, education, and lesion load, and corrected for multiple comparisons. False discovery rate (FDR) was used for the correction of multiple comparisons. RESULTS: Bilateral FAT FA showed significant association with phonemic verbal fluency task (Left; r = 0.46, p = 0.0058 and right; r = 0.46, p = 0.0059) but not semantic fluency task and this relation remained significant after FDR correction (p = 0.02 bilaterally). Although left AF showed some significant association with phonemic fluency task, this relation was insignificant after FDR correction. CONCLUSION: We show that bilateral FAT are correlates of phonemic verbal fluency task but not semantic in an MS cohort with cognitive impairment. This finding suggests that FAT is more specialized in lexical retrieval function as semantic fluency test encompasses all the functions except the lexical retrieval.

A direct visuosensory cortical connectivity of the human limbic system. Dissecting the trajectory of the parieto-occipito-hypothalamic tract in the human brain using diffusion weighted tractography.

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.