White Matter Connectivity In Patients Research Articles

Cerebral White Matter Connectivity in Adolescent Idiopathic Scoliosis: A Diffusion Magnetic Resonance Imaging Study.

Adolescent idiopathic scoliosis (AIS) is characterized by the radiographic presence of a frontal plane curve, with a magnitude greater than 10° (Cobb technique). Diffusion MRI can be employed to assess the cerebral white matter. The aim of this study was to analyze, by means of MRI, the presence of any alteration in the connectivity of cerebral white matter in AIS patients. In this study, 22 patients with AIS participated. The imaging protocol consisted in T1 and diffusion-weighted acquisitions. Based on the information from one of the diffusion acquisitions, a whole brain tractography was performed with the MRtrix tool. Tractography is a method to deduce the trajectory of fiber bundles through the white matter based on the diffusion MRI data. By combining cortical segmentation with tractography, a connectivity matrix of size 84 × 84 was constructed using FA (fractional anisotropy), and the number of streamlines as connectomics metrics. The results obtained support the hypothesis that alterations in cerebral white matter connectivity in patients with adolescent idiopathic scoliosis (AIS) exist. We consider that the application of diffusion MRI, together with transcranial magnetic stimulation neurophysiologically, is useful to search the etiology of AIS.

Hippocampal Subfields and White Matter Connectivity in Patients with Subclinical Geriatric Depression.

Despite an abundance of research related to the functional and structural changes of the brain in patients with geriatric depression, knowledge related to early alterations such as decreased white matter connectivity and their association with cognitive decline remains lacking. We aimed to investigate early alterations in hippocampal microstructure and identify their associations with memory function in geriatric patients with subclinical depression. Nineteen participants with subclinical geriatric depression and 19 healthy controls aged ≥65 years exhibiting general cognitive function within the normal range were included in the study and underwent assessments of verbal memory. Hippocampal subfield volumes were determined based on T1-weighted magnetization-prepared rapid gradient echo (T1-MPRAGE) images, while group tractography and connectometry analyses were conducted using diffusion tensor images. Our findings indicated that the volumes of whole bilateral hippocampus, cornus ammonis (CA) 1, molecular layer, left subiculum, CA3, hippocampal tail, right CA4, and granule cell/molecular layers of the dentate gyrus (GC-ML-DG) were significantly smaller in the subclinical depression group than in the control group. In the subclinical depression group, verbal learning was positively correlated with the volumes of the CA1, GC-ML-DG, molecular layer, and whole hippocampus in the right hemisphere. The fractional anisotropy of the bilateral fornix was also significantly lower in the subclinical depression group and exhibited a positive correlation with verbal learning and recall in both groups. Our results suggest that hippocampal microstructure is disrupted and associated with memory in patients with subclinical depression.

White matter microstructural differences between right and left mesial temporal lobe epilepsy.

Mesial temporal lobe epilepsy (mTLE) is a chronic focal epileptic disorder characterized by recalcitrant seizures often necessitating surgical intervention. Identifying the laterality of seizure focus is crucial for pre-surgical planning. We implemented diffusion MRI (DMRI) connectometry to identify differences in white matter connectivity in patients with left and right mTLE relative to healthy control subjects. We enrolled 12 patients with right mTLE, 12 patients with left mTLE, and 12 age/sex matched healthy controls (HCs). We used DMRI connectometry to identify local connectivity patterns of white matter tracts, based on quantitative anisotropy (QA). We compared QA of white matter to reconstruct tracts with significant difference in connectivity between patients and HCs and then between patients with left and right mTLE. Right mTLE patients show higher anisotropy in left inferior longitudinal fasciculus (ILF) and forceps minor and lower QA in genu of corpus callosum (CC), bilateral corticospinal tracts (CSTs), and bilateral middle cerebellar peduncles (MCPs) compared to HCs. Left mTLE patients show higher anisotropy in genu of CC, bilateral CSTs, and right MCP and decreased anisotropy in forceps minor compared to HCs. Compared to patients with right mTLE, left mTLE patients showed increased and decreased connectivity in some major tracts. Our study showed the pattern of microstructural disintegrity in mTLE patients relative to HCs. We demonstrated that left and right mTLE patients have discrepant alternations in their white matter microstructure. These results may indicate that left and right mTLE have different underlying pathologic mechanisms.

Altered white matter connectivity in patients with schizophrenia: An investigation using public neuroimaging data from SchizConnect.

Several studies have produced extensive evidence on white matter abnormalities in schizophrenia (SZ). However, optimum consistency and reproducibility have not been achieved, and reported low white matter tract integrity in patients with SZ varies between studies. A whole-brain imaging study with a large sample size is needed. This study aimed to investigate white matter integrity in the corpus callosum and connections between regions of interests (ROIs) in the same hemisphere in 122 patients with SZ and 129 healthy controls with public neuroimaging data from SchizConnect. For each diffusion-weighted image (DWI), two-tensor full-brain tractography was performed; DWIs were parcellated by processing and registering T1 images with FreeSurfer and Advanced Normalization Tools. White matter query language was used to extract white matter fiber tracts. We evaluated group differences in means of diffusion measures between the patients and controls, and correlations of diffusion measures with the severity of clinical symptoms and cognitive impairment in the patients using the Positive and Negative Syndrome Scale (PANSS), a letter-number sequencing (LNS) test, vocabulary test, letter fluency test, category fluency test, and trail-making test, part A. To correct for multiple comparisons, a false discovery rate of q < 0.05 was applied. In patients with SZ, we observed significant radial diffusivity (RD) and trace (TR) increases in left thalamo-occipital tracts and the right uncinate fascicle, and a significant RD increase in the right middle longitudinal fascicle (MDLF) and the right superior longitudinal fascicle ii. Correlations were present between TR of left thalamo-occipital tracts, and the letter fluency test and the LNS test, and RD in the right MDLF and PANSS positive subscale score. However, these correlations were not significant after correction for multiple comparisons. These results indicated widespread white matter fiber tract abnormalities in patients with SZ, contributing to SZ pathophysiology.

Effects of Uric Acid on the Alterations of White Matter Connectivity in Patients with Major Depression.

Uric acid is a non-enzymatic antioxidant associated with depression. Despite its known protective role in other brain disorders, little is known about its influence on the structural characteristics of brains of patients with major depressive disorder (MDD). This study explored the association between uric acid and characteristics of white matter (WM) in patients with MDD.A total of 32 patients with MDD and 23 healthy controls (HCs) were examined. All participants were scored based on the Beck Depression Inventory and Beck Anxiety Inventory at baseline. All patients were also rated with the Hamilton Depression Rating Scale. We collected blood samples from all participants immediately after their enrollment and before the initiation of antidepressants in case of patients. Tract-based spatial statistics were used for all imaging analyses.Lower fractional anisotropy (FA) and higher radial diffusivity (RD) values were found in the MDD group than in the HC group. Voxelwise correlation analysis revealed that the serum uric acid levels positively correlated with the FA and negatively with the RD in WM regions that previously showed significant group differences in the MDD group. The correlated areas were located in the left anterior corona radiata, left frontal lobe WM, and left anterior cingulate cortex WM.The present study suggests a significant association between altered WM connectivity and serum uric acid levels in patients with MDD, possibly through demyelination.

Effects of Uric Acid on the Alterations of White Matter Connectivity in Patients with Major Depression.

Objective Uric acid is a non-enzymatic antioxidant associated with depression. Despite its known protective role in other brain disorders, little is known about its influence on the structural characteristics of brains of patients with major depressive disorder (MDD). This study explored the association between uric acid and characteristics of white matter (WM) in patients with MDD. Methods A total of 32 patients with MDD and 23 healthy controls (HCs) were examined. All participants were scored based on the Beck Depression Inventory and Beck Anxiety Inventory at baseline. All patients were also rated with the Hamilton Depression Rating Scale. We collected blood samples from all participants immediately after their enrollment and before the initiation of antidepressants in case of patients. Tract-based spatial statistics were used for all imaging analyses. Results Lower fractional anisotropy (FA) and higher radial diffusivity (RD) values were found in the MDD group than in the HC group. Voxelwise correlation analysis revealed that the serum uric acid levels positively correlated with the FA and negatively with the RD in WM regions that previously showed significant group differences in the MDD group. The correlated areas were located in the left anterior corona radiata, left frontal lobe WM, and left anterior cingulate cortex WM. Conclusion The present study suggests a significant association between altered WM connectivity and serum uric acid levels in patients with MDD, possibly through demyelination.

Differential effect of COMT gene methylation on the prefrontal connectivity in subjects with depression versus healthy subjects

Expression of the catechol-O-methyl transferase (COMT) gene mainly determines prefrontal dopaminergic availability. Deficient prefrontal dopaminergic activity leads to loss of interest, energy, and motivation, which are core symptoms of depression. Given the role of stress-environmental interactions in major depressive disorder (MDD), we investigated the impact of COMT gene methylation status on prefrontal connectivity. We measured COMT gene methylation and polymorphisms (Val158Met) at the rs4468 locus in peripheral blood samples of healthy controls (n = 90) and patients with MDD (n = 90). We used diffusion tensor imaging to calculate the fractional anisotropy (FA) and radial diffusivity (RD) of the white matter tracts related to prefrontal cortex. Finally, we examined the effects of COMT gene methylation on the white matter connectivity in patients with MDD. The FA and RD values in the prefrontal white matter tracts of patients with MDD were positively and negatively associated with COMT gene methylation, respectively. In the control group, on the other hand, the association between white matter connectivity and COMT gene methylation showed opposite pattern to those of MDD. COMT gene methylation has a substantial effect on the prefrontal connectivity in patients with MDD. Moreover, COMT gene methylation and prefrontal connectivity showed opposite relationships in patients and controls. Thus, stress-related alterations in dopaminergic neurotransmission have a differential effect on white matter connectivity according to the microenvironment in the brain.

Disrupted thalamo-orbitofrontal but not fronto-temporal white matter connectivity in people with schizotypal personality disorder

IntroductionDespite patients with schizophrenia showed the deficits in the fronto-temporal and thalamo-frontal connectivity, the white matter connectivity in patients with schizotypal personality disorder had not been systemically investigated.MethodsThis study involved 40 neuroleptic-naïve patients with schizotypal personality disorder (SPD), 60 patients with schizophrenia (SCZ), and 100 healthy controls (HC), and scanned on the 3T MRI scanner. Probablistic tractography was performed using the FATCAT software in AFNI. The target brain regions (bilateral lateral frontal, medial frontal, orbitofrontal, temporal and thalamus) were extracted from the automated segmentation and cortical parcellation. Cross-sectional comparisons in mean fractional anisotropy (FA) performed on the thalamo-lateral frontal, thalamo-medial frontal, thalamo-orbitofrontal, lateral frontal-temporal and orbitofrontal-temporal pathway. We also analyzed the relationship between the white matter pathway and the Positive and Negative Syndrome Scale and GAF.ResultsThe diffusion tensor imaging showed that SCZ and SPD had decreased FA in the left thalamo-orbitofrontal pathway. However, SPD showed no alteration in the fronto-temporal pathway, despite SCZ showed decreased FA in the left temporo-orbitofrontal pathway. In SCZ, there were significant correlations between FA value in the left temporo-orbitofrontal pathway and negative symptoms score in PANSS and GAF score. However, SPD showed the trend level relationship between the GAF score and FA value in the left temporo-orbitofrontal pathway.ConclusionThese results suggest that the deficits in thalamo-frontal connectivity may be a trait marker of schizophrenia spectrum disorder, and the deficits in fronto-temporal connectivity may play a key role towards the vulnerability of psychosis.Disclosure of interestThe authors have not supplied their declaration of competing interest.

P.1.i.011 The effects of the VRK2 (rs2312147) gene on white matter connectivity in patients with schizophrenia

High power of pre-stimulus cortical alpha rhythms (about 8–12 Hz) underlies conscious perception in normal subjects. Here we tested the hypothesis that these rhythms are abnormal in persistent vegetative state (PVS) patients, who are awake but not aware of self and environment.Clinical and resting-state, eyes-closed electroencephalographic (EEG) data were taken from a clinical archive. These data were recorded in 50 PVS subjects (level of cognitive functioning – LCF score: I–II) and in 30 cognitively normal subjects. Rhythms of interest were delta (2–4 Hz), theta (4–8 Hz), alpha 1 (8–10.5 Hz), alpha 2 (10.5–13 Hz), beta 1 (13–20 Hz), and beta 2 (20–30 Hz). Cortical sources were estimated by low-resolution electromagnetic tomography (LORETA). Based on LCF score at 3-months follow-up, PVS patients were retrospectively divided into three groups: 30 subjects who did not recover (NON-REC patients; follow-up LCF: I–II), 8 subjects classified as minimally conscious state patients (MCS patients; follow-up LCF: III–IV), and 12 subjects who recovered (REC patients; follow-up LCF: V–VIII).Occipital source power of alpha 1 and alpha 2 was high in normal subjects, low in REC patients, and practically null in NON-REC patients. A Cox regression analysis showed that the power of alpha source predicted the rate of the follow up recovery, namely the higher its power, the higher the chance to recover consciousness. Furthermore, the MCS patients showed intermediate values of occipital alpha source power between REC and NON-REC patients.These results suggest that cortical sources of alpha rhythms are related to the chance of recovery at a 3-months follow-up in patients in persistent vegetative state.Cortical sources of resting alpha rhythms might predict recovery in PVS patients.

Effects of VRK2 (rs2312147) on white matter connectivity in patients with schizophrenia.

Recent genome-wide association studies of schizophrenia reported a novel risk variant, rs2312147 at vaccinia-related kinase 2 gene (VRK2), in multiple Asian and European samples. However, its effect on the brain structure in schizophrenia is little known. We analyzed the brain structure of 36 schizophrenia patients and 18 healthy subjects with regard to rs2312147 genotype groups. Brain magnetic resonance scans for gray matter (GM) and white matter (WM) analysis, and genotype analysis for VRK2 rs2312147, were conducted. The Positive and Negative Syndrome Scale and the Digit Symbol Test were assessed for schizophrenia patients. There was no significant difference in either GM volume or WM connectivity with regard to rs2312147 genotype in healthy subjects. In contrast, we found significant differences in the WM connectivity between rs2312147 CC and CT/TT genotype groups of schizophrenia patients. The related brain areas included the splenium of corpus callosum, the left occipital lobe WM, the internal capsule (left anterior limb and right retrolenticular part), the bilateral temporal lobe WM, the left fornix/stria terminalis, the left cingulate gyrus WM, and the left parietal lobe WM. Voxelwise correlation analysis revealed that the Digit Symbol Test scores (age corrected) correlated with the fractional anisotropy in WM tracts that previously showed significant group differences between the CT/TT and CC genotypes in the rs2312147 CT/TT genotype group, while no significant correlation was found in the CC genotype group. Our data may provide evidence for the effect of VRK2 on WM connectivity in patients with schizophrenia.

Effect of the COMT val158met polymorphism on white matter connectivity in patients with major depressive disorder

Cortico-limbic network dysfunction and genetic polymorphism are considered to be associated with major depressive disorder (MDD). Using diffusion tensor imaging (DTI), we investigated the relationship between catechol-O-methyltransferase (COMT) gene polymorphisms and white matter tract integrity in patients with MDD. Eighty-six patients with MDD and 62 healthy controls participated in this study. DTI and genotyping for the COMT val158met gene (rs4680) polymorphism were conducted to determine the impact of COMT polymorphisms on white matter changes in patients with MDD. Voxel-wise statistical analyses of fractional anisotropy (FA) were performed using tract-based spatial statistics (TBSS). FAs of the MDD patient group were significantly decreased in bilateral frontal forceps minor, bilateral anterior cingulum, genu of corpus callosum, left posterior cingulum, right superior longitudinal fasciculus, and right posterior thalamic radiation compared with those of healthy controls. In the MDD patient group, mean FA in subjects with the GG allele was significantly decreased in left inferior longitudinal fasciculus, bilateral middle temporal gyrus, right frontal gyrus, and right cingulum bundle area compared with subjects with the AA/AG allele. These findings suggest cortico-limbic network dysfunction in MDD. Specifically, further FA reduction was evident in MDD patients with the valine homozygote group of the COMT gene. MDD may be associated with dysfunctional white matter changes, and the valine homozygote of COMT gene may contribute to further abnormalities in these pathological changes.

The effects of the catechol-O-methyltransferase val158met polymorphism on white matter connectivity in patients with panic disorder

BackgroundThe catechol-O-methyltransferase (COMT) gene val158met polymorphism (rs4680) has been found to be associated with various psychiatric phenotypes including panic disorder. Considering the probable genetic influence of COMT on the pathogenesis of panic disorder and white matter connectivity, the present study investigated white matter connectivity using diffusion tensor imaging in relation to the COMT genotype in panic disorder. MethodsTwenty-six patients with panic disorder and twenty-six age- and gender-matched healthy controls participated in this study. Brain magnetic resonance scans and genotype analysis for COMT rs4680 were conducted. Panic Disorder Severity Scale, Albany Panic and Phobia Questionnaire, and Anxiety Sensitivity Inventory-Revised were assessed. Tract-based spatial statistics (TBSS) were used for image analysis. ResultsThere was no significant difference in white matter analysis between panic disorder and healthy controls. However, TBSS analysis showed increased fractional anisotropy (FA) in posterior thalamic radiation, posterior and superior corona radiata, superior longitudinal fasciculus, and sagittal stratum, all located in the right hemisphere in COMT AA/AG genotype group compared to GG genotype in panic disorder. Voxelwise correlational analysis revealed the symptom severity scores are correlated with the FA in white matter tracts that previously showed significant group differences between AA/AG and GG genotypes in COMT AA/AG genotype group, while no significant correlation was found in GG genotype group. LimitationsThe sample size in each group was small, hence, further studies with larger numbers of patients are needed to confirm our findings. ConclusionsThese data suggested that COMT rs4680 could affect the white matter connectivity in panic disorder.

Disrupted Topological Organization in White Matter Structural Networks in Amnestic Mild Cognitive Impairment: Relationship to Subtype

To investigate the topological alterations of whole-brain white matter structural connectivity in patients with different types of amnestic mild cognitive impairment (aMCI), including single-domain (SD) and multidomain (MD) aMCI, and to explore the relationship of such connectivity with neuropsychologic performance. This study was approved by the institutional review board of Imaging Center for Brain Research, Beijing Normal University. Written informed consent was obtained from each participant. The present study involved 38 patients with aMCI (SD aMCI, n=18; MD aMCI, n=20) and 36 age- and sex-matched healthy control subjects. White-matter connectional architecture in each participant was depicted with diffusion-weighted MR imaging and represented in terms of a connectivity matrix by using a deterministic tractography method. Graph theory-based analyses were then performed to characterize brain network properties. The global topological organization of white matter networks was significantly disrupted in patients with MD aMCI (P<.01 for all) but not in those with SD aMCI, as compared with control subjects. Connectivity impairment in patients with MD aMCI was found in the temporal, frontal, and parietal cortices (P<.05, corrected). MD aMCI had decreased network efficiency relative to SD aMCI (P=.016), with the most pronounced differences located in the frontal cortex (P<.01 for all). Strong associations between cognitive impairments and disrupted topological features (global, P<.05; regional, P<.002) were identified in patients with aMCI. The present study suggests early onset disruption of whole-brain white matter connectivity in patients with aMCI, especially in those with the MD subtype, supporting the view that MD aMCI is a more advanced form of disease than is SD aMCI. Moreover, cognitive correlations with topological network properties suggest their potential use as markers to assess the risk of Alzheimer disease.