Uncinate Fasciculus In Patients Research Articles

Reduced myelin density in unmedicated major depressive disorder: An inhomogeneous magnetization transfer MRI study

ObjectivesTo detect the whole-brain reduced myelin density in unmedicated patients with major depressive disorder (MDD) using the inhomogeneous magnetization transfer (ihMT) imaging technology. Compared to other technologies, the ihMT provides high specificity and sensitivity to detect myelin. MethodIn this prospective study, fifty unmedicated patients (mean age 25.36 years, 40% men) with MDD and 57 age- and sex-matched healthy controls (HCs) (mean age 25.02 years, 53% men) were recruited between January 2019 and December 2019. All participants underwent ihMT imaging, and pseudo-quantitative ihMT (qihMT) and ihMT ratio (ihMTR) were obtained. The mean values of qihMT and ihMTR extracted from the 50 WM masks (extracted from the International Consortium for Brain Mapping, ICBM-152) in each participant were compared between participants in the MDD and HCs groups. The symptoms of patients were evaluated using the 24-item Hamilton Depression Rating scale (HDRS). ResultsCompared with the HC group, the MDD group showed significantly decreased qihMT and ihMTR values in the left inferior fronto-occipital fasciculus (IFOF) (t = -4.057, p < 0.001; t = -3.662, p < 0.001) and the left uncinate fasciculus (UF) (t = -4.776, p < 0.001; t = -3.800, p < 0.001) after Bonferroni correction. The correlation analysis displayed a significant negative correlation between qihMT values of the left IFOF and HDRS total scores in patients with MDD (r = -0.390, p = 0.012). LimitationsThis was a cross-sectional study with a relative small sample. ConclusionsThese findings suggest the reduced myelin density in the IFOF and UF in patients with MDD, which might be associated with the pathophysiology of MDD.

Asymmetric alterations of white matter integrity in patients with insomnia disorder.

Despite the adverse consequences of insomnia disorder for both individuals and society, the underlying neurobiological processes are poorly understood. The purpose was to further understand the alterations of white matter tracts in patients with insomnia and their association with sleep variables and also to determine if diffusion tensor imaging measures would be a useful disease marker. Twenty-six patients with insomnia and 26 age-matched healthy volunteers underwent diffusion tensor imaging. We employed an automated probabilistic tractography analysis approach using TRActs Constrained by UnderLying Anatomy (TRACULA) to quantify diffusion measures in major white matter tracts. We found significantly increased fractional anisotropy in the right cingulum-angular bundle and uncinate fasciculus in patients group compared to controls. Moreover, the mean diffusivity and radial diffusivity were reduced in the right cingulum-angular bundle in patients group in comparison with controls. We also found significantly increased fractional anisotropy along the bilateral cingulum-angular bundle and right uncinate fasciculus in patients. Also, mean and radial diffusivity were reduced along the right cingulum-angular bundle in patients group compared to controls. There is a significant positive correlation between fractional anisotropy and Epworth Sleepiness Scale scores. Moreover, there are negative correlations between mean, radial and axial diffusivity and total sleep time and sleep efficiency and also positive correlations between mean, radial and axial diffusivity and duration of disease and Pittsburgh Sleep Quality Index scores. This study showed theimportanceof examining whole-tract and waypoint white matter integrity in insomnia disorder. We found asymmetric widespread white matter integrity changes in patients with insomnia.

Characteristics of the Uncinate Fasciculus and Cingulum in Patients with Mild Cognitive Impairment: Diffusion Tensor Tractography Study.

Many studies have examined the relationship between cognition, and the cingulum and uncinate fasciculus (UF). In this study, diffusion tensor tractography (DTT) was used to investigate the correlation between fractional-anisotropy (FA) values and the number of fibers in the cingulum and UF in patients with and without cognitive impairment. The correlation between cognitive function, and the cingulum and UF was also investigated. Thirty patients (14 males, age = 70.68 ± 7.99 years) were divided into a control group (n = 14) and mild-cognitive-impairment (MCI) group (n = 16). The Seoul Neuropsychological Screening Battery (SNSB) and DTT were performed to assess cognition and bilateral tracts of the cingulum and UF. The relationship between SNSB values and the cingulum and UF was analyzed. The number of fibers in the right cingulum and right UF were significantly different between the two groups. The MCI group showed thinner tracts in both the cingulum and UF compared to the control group. A significant relationship was found between the number of fibers in the right UF and delayed memory recall. In conclusion, memory loss in MCI was associated with a decreased number of fibers in the right UF, while language and visuospatial function were related to the number of fibers in the right cingulum.

Localizing deficits in white matter tracts of patients with narcolepsy with cataplexy: tract-specific statistical analysis.

White matter alterations related to hypocretin pathway have been less evaluated in patients who have narcolepsy with cataplexy (NC), as compared to the identified exploration of gray matter and have varied among structural brain magnetic resonance imaging studies. The aim of this study was to investigate the disruption of specific white matter tracts in drug-naïve patients with NC, by using a tract-specific statistical analysis (TSSA). Forty drug-naïve NC patients with cataplexy and 42 heathy controls were enrolled in the study. All participants completed diffusion weighted imaging, polysomnography, and neuropsychological testing. At that time, we automatically identified fourteen major fiber tracts using diffusion tensor imaging techniques and analyzed the group comparison of fractional anisotropy (FA) values for each tract between the NC and controls, controlling for the participant's age and gender. The mean age of the NC patients was 26.9years and the onset age of daytime sleepiness and cataplexy was 16.7years and 19.9years, respectively. Relative to the controls, the NC patients showed that there were identified decreased FA values in the bilateral inferior fronto-occipital fasciculus (IFO). The Epworth sleepiness scale was positively correlated with FA values for the left IFO and right cingulate. The REM sleep latency was positively correlated with FA values for the left IFO, cingulate, and uncinate fasciculus in patients. This TSSA study revealed disintegration of the IFO in the NC patients and suggested that disintegration of WM tracts connected to the frontal cortex contributes to clinical manifestations of narcolepsy.

Uncinate fasciculus connectivity in patients with psychogenic nonepileptic seizures: A preliminary diffusion tensor tractography study

The amygdala, hippocampus, and medial prefrontal cortex are limbic brain regions connected by the uncinate fasciculus (UF) and implicated in emotion regulation. The aim of this study was to assess the connectivity characteristics of the UF in patients with psychogenic nonepileptic seizures (PNES) and matched healthy controls. We hypothesized that white matter connectivity of the UF in patients with PNES would differ from that in healthy controls. Eight patients with PNES and eight age- and sex-matched healthy controls underwent 3T MRI and 32-direction diffusion tensor imaging (DTI). Computation of DTI indices including fractional anisotropy (FA) and diffusion tensor tractography was performed. Two regions of interest were defined to manually trace the UF in each hemisphere for each subject. Fractional anisotropy and the number of reconstructed streamlines for the left and right hemispheres of the UF and the degree of asymmetry for each measure were compared between groups. Correlations between UF measures and clinical variables were also performed. Patients with PNES exhibited a significantly greater number of UF streamlines in the right hemisphere tract than in the left hemisphere (p=0.031), with such difference not observed in controls (p=0.81). This was reflected in a significant group difference in the asymmetry index (AI) for the number of streamlines, with more rightward asymmetry in patients with PNES (p=0.021). Average FA of the UF was similar between groups and between hemispheres for each group (all p>0.05). Age at illness onset was correlated with the AI for FA (r=−0.87; p=0.0045). Previously observed differences in emotion processing between controls and patients with PNES may be related to the differences in the rightward asymmetry in the number of UF streamlines in patients with PNES. Age at PNES onset appears to also have a role in the FA asymmetry of the UF. This is the first study to investigate the structural connectivity in these regions involved in emotional regulation in patients with PNES; further research is necessary to clarify the complex relationships between clinical measures and DTI characteristics.

Diffusion tensor tract-specific analysis of the uncinate fasciculus in patients with progressive supranuclear palsy

The uncinate fasciculus (UF), a major white-matter tract connecting the frontal and temporal lobes, is related to cognitive/behavioral function. Recently, the UF has been suggested to constitute an indirect pathway of the "semantic ventral pathway" in association with the inferior longitudinal fasciculus (ILF). This retrospective study aimed to evaluate damage to the UF and ILF in patients with progressive supranuclear palsy (PSP) using diffusion tensor tract-specific analysis. Diffusion tensor imaging (DTI) of 16 PSP patients with Richardson's syndrome (PSP-RS) and 21 age-matched volunteers were obtained. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values for the bilateral UF and ILF were calculated by tract-specific analysis. Student's t test was used to evaluate the differences between the patients and controls. Also, voxel-based morphometry (VBM) was performed using 3D T1-weighted images to explore the regional atrophy of gray matter in the patients. In patients with PSP-RS, FA of the left UF was significantly decreased compared with the controls, while significant increases in ADC were found in the UF and ILF bilaterally. VBM analysis showed significant clusters of reduced gray matter in the frontal cortex (predominantly in the lateral orbitofrontal cortex, pars opercularis and mesial frontal cortex) and subcortical nuclei (midbrain, caudate and thalamic). This study has shown that patients with PSP-RS had impairment of the UF and ILF. Damage to the UF is thought to be related to atrophy of the orbitofrontal cortex and may possibly be correlated with the cognitive/behavioral impairment seen in PSP.

1269 – Reduced fractional anisotropy in the uncinate fasciculus in patients with major depression carrying the met-allele of the Val66Met brain-derived neurotrophic factor genotype

Experimental studies support a neurotrophic hypothesis of major depressive disorder (MDD). The aim of this study was to determine the effect of Val66Met brain derived neurotrophic factor (BDNF) polymorphism on the white matter fibre tracts connecting hippocampus and amygdala with the prefrontal lobe in a sample of patients with MDD and healthy controls. Thirty seven patients with MDD and 42 healthy volunteers were recruited. Diffusion tensor imaging (DTI) data with 61 diffusion directions were obtained with MRI 3 Tesla scanner. Deterministic tractography was applied with ExploreDTI and Val66Met BDNF SNP (rs6265) was genotyped. Fibre tracts connecting the hippocampus and amygdala with the prefrontal lobe, namely uncinate fasciculus, fornix and cingulum were analysed. A significant interaction was found in the uncinate fasciculus (UF) between BDNF alleles and diagnosis. Patients carrying the BDNF met-allele had smaller fractional anisotropy (FA) in the UF compared to those patients homozygous for valallele and compared to healthy subjects carrying the met-allele. A significant 3-way interaction was detected between region of the cingulum (dorsal, rostral and parahippocampal regions), brain hemisphere and BDNF genotype. Larger FA was detectable in the left rostral cingulum for met-allele carriers when compared to val/val alelle carriers. We provide evidence for the importance of the neurotrophic involvement in limbic and prefrontal connections. The met-allele of the BDNF polymorphism seems to render subjects more vulnerable for dysfunctions associated with the UF, a tract known to be related to negative emotional-cognitive processing bias, declarative memory problems, and autonoetic self awareness.

Neural injury of uncinate fasciculus in patients with diffuse axonal injury

The recent development of diffusion tensor imaging (DTI) allows visualization and estimation of the uncinate fasciculus (UF). We investigated injuries of the UF in patients with diffuse axonal injury (DAI) who showed no specific lesions except for DAI lesions on conventional brain MRI. Twenty-one chronic patients with DAI, and 21 age- and sex-matched normal control subjects were recruited for this study. Diffusion tensor images were acquired using a sensitivity-encoding head coil at 1.5 T and the UF was reconstructed using DTI-Studio software. Fractional anisotropy (FA), apparent diffusion coefficient (ADC) value, and fiber number of the UF were measured. In the DAI group, the FA values and fiber numbers were significantly decreased compared to those of the control group (P< 0.05). The FA value and fiber number decreased 8.4% and 26.5% in the DAI group compared to those of the control group. By contrast, the ADC value did not show any difference between the DAI and control groups (P> 0.05). Changes in the DTI parameters of the DAI group appeared to indicate neural injury of the UF. We believe that DTI can be a useful evaluation tool for detecting hidden neural injuries of UF in patients with DAI.

Reduced fractional anisotropy in the uncinate fasciculus in patients with major depression carrying the met‐allele of the Val66Met brain‐derived neurotrophic factor genotype

Experimental studies support a neurotrophic hypothesis of major depressive disorder (MDD). The aim of this study was to determine the effect of Val66Met brain-derived neurotrophic factor (BDNF) polymorphism on the white matter fiber tracts connecting hippocampus and amygdala with the prefrontal lobe in a sample of patients with MDD and healthy controls. Thirty-seven patients with MDD and 42 healthy volunteers were recruited. Diffusion tensor imaging (DTI) data with 61 diffusion directions were obtained with MRI 3 Tesla scanner. Deterministic tractography was applied with ExploreDTI and Val66Met BDNF SNP (rs6265) was genotyped. Fiber tracts connecting the hippocampus and amygdala with the prefrontal lobe, namely uncinate fasciculus (UF), fornix, and cingulum were analyzed. A significant interaction was found in the UF between BDNF alleles and diagnosis. Patients carrying the BDNF met-allele had smaller fractional anisotropy (FA) in the UF compared to those patients homozygous for val-allele and compared to healthy subjects carrying the met-allele. A significant three-way interaction was detected between region of the cingulum (dorsal, rostral, and parahippocampal regions), brain hemisphere and BDNF genotype. Larger FA was detectable in the left rostral cingulum for met-allele carriers when compared to val/val alelle carriers. We provide evidence for the importance of the neurotrophic involvement in limbic and prefrontal connections. The met-allele of the BDNF polymorphism seems to render subjects more vulnerable for dysfunctions associated with the UF, a tract known to be related to negative emotional-cognitive processing bias, declarative memory problems, and autonoetic self awareness.

White matter alterations in social anxiety disorder

White matter architecture in patients with social anxiety disorder (SAD) has rarely been investigated, but may yield insights with respect to altered structural brain connectivity. Initial evidence points to alterations in the uncinate fasciculus (UF). We applied diffusion tensor imaging in 25 patients with SAD and 25 matched healthy subjects. Whole-brain fractional anisotropy (FA) maps were used for group comparison and voxel-wise correlation with psychometric and clinical measures. Additionally, a region-of-interest analysis of the UF was performed. Patients with SAD had reduced FA compared to healthy subjects in or near the left UF and the left superior longitudinal fasciculus. There were no regions with increased FA in SAD. In the region-of-interest analysis, a negative correlation between FA and trait anxiety was identified in the left and right UF in patients, but not in healthy subjects. No correlations with social anxiety scores were observed. The present study partially confirms previous results pointing to frontal WM alterations in or near the UF in patients with SAD. SAD-specific dimensional associations of FA with trait anxiety might reflect general pathological and/or compensatory mechanisms as a function of symptom severity in patients. Future studies should disentangle in which way the identified WM alterations match functional alterations.

Diffusion tensor tract-specific analysis of the uncinate fasciculus in patients with amyotrophic lateral sclerosis

The uncinate fasciculus (UF) consists of core fibers connecting the frontal and temporal lobes and is considered to be related to cognitive/behavioral function. Using diffusion tensor tractography, we quantitatively evaluated changes in fractional anisotropy (FA) and the apparent diffusion coefficient (ADC) of the UF by tract-specific analysis to evaluate the damage of the UF in patients with amyotrophic lateral sclerosis (ALS). We obtained diffusion tensor images of 15 patients with ALS and 9 age-matched volunteers. Patients with ALS showed significantly lower mean FA (P = 0.029) compared with controls. No significant difference was seen in mean ADC. The results suggest that damage of the UF in patients with ALS can be quantitatively evaluated with FA.

White matter abnormalities in bipolar disorder and schizophrenia detected using diffusion tensor magnetic resonance imaging

Strong qualitative and quantitative evidence exists of white matter abnormalities in both schizophrenia and bipolar disorder (BD). Diffusion tensor imaging (DTI) studies suggest altered connectivity in both disorders. We aim to address the diagnostic specificity of white matter abnormalities in these disorders. DTI was used to assess white matter integrity in clinically stable patients with familial BD (n = 42) and familial schizophrenia (n = 28), and in controls (n = 38). Differences in fractional anisotropy (FA) were measured using voxel-based morphometry and automated region of interest analysis. Reduced FA was found in the anterior limb of the internal capsule (ALIC), anterior thalamic radiation (ATR), and in the region of the uncinate fasciculus in patients with BD and those with schizophrenia compared with controls. A direct comparison between patient groups found no significant differences in these regions. None of the findings were associated with psychotropic medication. Reduced integrity of the ALIC, uncinate fasciculus, and ATR regions is common to both schizophrenia and BD. These results imply an overlap in white matter pathology, possibly relating to risk factors common to both disorders.

Tract-based Analysis of Magnetization Transfer Ratio and Diffusion Tensor Imaging of the Frontal and Frontotemporal Connections in Schizophrenia

In the pathophysiology of schizophrenia, aberrant connectivity between brain regions may be a central feature. Diffusion tensor imaging (DTI) studies have shown altered fractional anisotropy (FA) in white brain matter in schizophrenia. Focal reductions in myelin have been suggested in patients using magnetization transfer ratio (MTR) imaging but to what extent schizophrenia may be related to changes in MTR measured along entire fiber bundles is still unknown. DTI and MTR images were acquired with a 1.5-T scanner in 40 schizophrenia patients and compared with those of 40 healthy participants. The mean FA and mean MTR were measured along the genu of the corpus callosum and the left and right uncinate fasciculus. A higher mean MTR of 1% was found in the right uncinate fasciculus in patients compared with healthy participants. A significant negative correlation between age and mean FA in the left uncinate fasciculus was found in schizophrenia patients but not in healthy participants. Decreased FA in the left uncinate fasciculus may be more prominent in patients with longer illness duration. The increased mean MTR in the right uncinate fasciculus could reflect a compensatory role for myelin in these fibers or possibly represent aberrant frontotemporal connectivity.