Effect of worry, depressed affect, and sensitivity to environmental stress owing to neurotic personality on MRI markers of cerebral small vessel disease: A univariable and multivariable Mendelian randomization study.

OBJECTIVE: Neuroticism was found to be associated with cerebral small vessel disease (CSVD) in observational studies. We aimed to explore the causal relationship between distinct components of neuroticism and CSVD. METHODS: Two-sample mendelian randomization (MR) study was conducted to explore the bidirectional causal relationships between three genetically distinct subclusters of neuroticism (depressed affect, worry, and sensitivity to environmental stress and adversity [SESA]) and MRI markers of CSVD using publicly available genome-wide association studies (GWAS) data. Inverse variance weighted (IVW) method was used for the primary causal estimates. Alternative MR approaches and extensive sensitivity analyses were conducted to ensure the robustness of the findings. Multivariable MR (MVMR) analysis was used to estimate the direct causal effects with adjustment of other known risk factors for CSVD. RESULTS: Genetically determined SESA was significantly associated with reduced fractional anisotropy (FA) (beta: -1.94, 95%CI: -3.04 to -0.84, p=5.29e-4), and associated with increased mean diffusivity (MD) (beta=1.55, 95%CI: 0.29 to 2.81, p=0.016) and white matter hyperintensities (WMH) (beta=0.25, 95% CI: 0.03 to 0.47, p=0.029) at the nominally significant level. MVMR analysis suggested the significant associations remained significant after accounting for body mass index (BMI), smoking, alcohol drinking, type 2 diabetes (T2D), hypertension, and depression. The other two neuroticism subclusters (depressed affect and worry) didn't have significant causal effects on the MRI markers. In the reverse MR analysis with the MRI markers as exposures, no significant associations were found. CONCLUSION: This study supported the casual role of SESA in the development of CSVD. Further research to explore the underlying mechanism are warranted.

Leptin bioavailability and markers of brain atrophy and vascular injury in the middle age.

INTRODUCTION: We investigated the associations of leptin markers with cognitive function and magnetic resonance imaging (MRI) measures of brain atrophy and vascular injury in healthy middle-aged adults. METHODS: We included 2262 cognitively healthy participants from the Framingham Heart Study with neuropsychological evaluation; of these, 2028 also had available brain MRI. Concentrations of leptin, soluble leptin receptor (sOB-R), and their ratio (free leptin index [FLI]), indicating leptin bioavailability, were measured using enzyme-linked immunosorbent assays. Cognitive and MRI measures were derived using standardized protocols. RESULTS: Higher sOB-R was associated with lower fractional anisotropy (FA, ß = -0.114 ± 0.02, p < 0.001), and higher free water (FW, ß = 0.091 ± 0.022, p < 0.001) and peak-width skeletonized mean diffusivity (PSMD, ß = 0.078 ± 0.021, p < 0.001). Correspondingly, higher FLI was associated with higher FA (ß = 0.115 ± 0.027, p < 0.001) and lower FW (ß = -0.096 ± 0.029, p = 0.001) and PSMD (ß = -0.085 ± 0.028, p = 0.002). DISCUSSION: Higher leptin bioavailability was associated with better white matter (WM) integrity in healthy middle-aged adults, supporting the putative neuroprotective role of leptin in late-life dementia risk. HIGHLIGHTS: Higher leptin bioavailability was related to better preservation of white matter microstructure. Higher leptin bioavailability during midlife might confer protection against dementia. Potential benefits might be even stronger for individuals with visceral obesity. DTI measures might be sensitive surrogate markers of subclinical neuropathology.

Improved cognition and preserved hippocampal fractional anisotropy in subjects undergoing carotid endarterectomy "CEA preserves cognition & hippocampal structure".

OBJECTIVES: A growing body of data indicates that extracranial carotid artery disease (ECAD) can contribute to cognitive impairment. However, there have been mixed reports regarding the benefit of carotid endarterectomy (CEA) as it relates to preserving cognitive function. In this work, diffusion magnetic resonance imaging (dMRI) and neurocognitive testing are used to provide insight into structural and functional brain changes that occur in subjects with significant carotid artery stenosis, as well as changes that occur in response to CEA. MATERIALS AND METHODS: The study design was a prospective, non-randomized, controlled study that enrolled patients with asymptomatic carotid stenosis. Thirteen subjects had severe ECAD (≥70% stenosis in at least one carotid artery) and were scheduled to undergo surgery. Thirteen had asymptomatic ECAD with <70% stenosis, therefore not requiring surgery. All subjects underwent neurocognitive testing using the Montreal Cognitive Assessment test (MoCA) and high angular resolution, multi-shell diffusion magnetic resonance imaging (dMRI) of the brain at baseline and at four-six months follow-up. Changes in MoCA scores as well as in Fractional anisotropy (FA) along the hippocampus were compared at baseline and follow-up. RESULTS: At baseline, FA was significantly lower along the ipsilateral hippocampus in subjects with severe ECAD compared to subjects without severe ECAD. MoCA scores were lower in these individuals, but this did not reach statistical significance. At follow-up, MoCA scores increased significantly in subjects who underwent CEA and remained statistically equal in control subjects that did not have CEA. FA remained unchanged in the CEA group and decreased in the control group. CONCLUSIONS: This study suggests that CEA improves cognition and preserves hippocampal white matter structure compared to control subjects not undergoing CEA.

Diffusion tensor metrics, motor and non-motor symptoms in de novo Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) is a neurodegenerative disorder characterized by dopaminergic neurons' degeneration of the substantia nigra, presenting with motor and non-motor symptoms. We hypothesized that altered diffusion metrics are associated with clinical symptoms in de novo PD patients. METHODS: Fractional Anisotropy (FA) and Mean (MD), Axial (AD), and Radial Diffusivity (RD) were assessed in 55 de novo PD patients (58.62 ± 9.85 years, 37 men) and 55 age-matched healthy controls (59.92 ± 11.25 years, 34 men). Diffusion-weighted images and clinical variables were collected from the Parkinson's Progression Markers Initiative study. Tract-based spatial statistics were used to identify white matter (WM) changes, and fiber tracts were localized using the JHU-WM tractography atlas. Motor and non-motor symptoms were evaluated in patients. RESULTS: We observed higher FA values and lower RD values in patients than controls in various fiber tracts (p-TFCE < 0.05). No significant MD or AD difference was observed between groups. Diffusion metrics of several regions significantly correlated with non-motor (state and trait anxiety and daytime sleepiness) and axial motor symptoms in the de novo PD group. No correlations were observed between diffusion metrics and other clinical symptoms evaluated. CONCLUSION: Our findings suggest microstructural changes in de novo PD fiber tracts; however, limited associations with clinical symptoms reveal the complexity of PD pathology. They may contribute to understanding the neurobiological changes underlying PD and have implications for developing targeted interventions. However, further longitudinal research with larger cohorts and consideration of confounding factors are necessary to elucidate the underlying mechanisms of these diffusion alterations in de novo PD.

The Role of Diffusion Tensor Imaging in CNS Tuberculosis.

Background and objective Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a significant global health concern, with India being a hotspot for the disease burden. Central nervous system (CNS) tuberculosis, though comprising a smaller proportion of total TB cases, is associated with significant morbidity and mortality. This study aimed to explore the utility of diffusion tensor imaging (DTI) in assessing the microstructural changes in white matter tracts associated with CNS tuberculosis. Materials and methods This study was conducted over two years at the All India Institute of Medical Sciences, Rishikesh. We employed a cross-sectional observational design and included patients with definite or highly probable tuberculous meningitis, alongside healthy controls. Results Our findings revealed a significant reduction in fractional anisotropy (FA) values in various white matter tracts of patients with CNS tuberculosis compared to healthy individuals. This reduction in FA correlated with the severity of tuberculous meningitis, particularly in the corpus callosum. Additionally, DTI highlighted distinct patterns of white matter involvement around intraparenchymal lesions, suggesting potential implications for clinical outcomes. The study emphasizes the utility of FA values in grading disease severity and prognosticating treatment outcomes in CNS tuberculosis. Conclusions Overall, this study provides valuable insights into the microstructural alterations in white matter tracts associated with CNS tuberculosis, highlighting the potential of DTI in early diagnosis, grading disease severity, and monitoring treatment response. We believe these findings will pave the way for further research to optimize the clinical management of this debilitating disease.

Additive effects of mild head trauma, blast exposure, and aging within white matter tracts: A novel Diffusion Tensor Imaging analysis approach.

Existing diffusion tensor imaging (DTI) studies of neurological injury following high-level blast exposure (hlBE) in military personnel have produced widely variable results. This is potentially due to prior studies often not considering the quantity and/or recency of hlBE, as well as co-morbidity with non-blast head trauma (nbHT). Herein, we compare commonly used DTI metrics: fractional anisotropy and mean, axial, and radial diffusivity, in Veterans with and without history of hlBE and/or nbHT. We use both the traditional method of dividing participants into 2 equally weighted groups and an alternative method wherein each participant is weighted by quantity and recency of hlBE and/or nbHT. While no differences were detected using the traditional method, the alternative method revealed diffuse and extensive changes in all DTI metrics. These effects were quantified within 43 anatomically defined white matter tracts, which identified the forceps minor, middle corpus callosum, acoustic and optic radiations, fornix, uncinate, inferior fronto-occipital and inferior longitudinal fasciculi, and cingulum, as the pathways most affected by hlBE and nbHT. Moreover, additive effects of aging were present in many of the same tracts suggesting that these neuroanatomical effects may compound with age.

Comparative Analysis of the Apparent Diffusion Coefficient and Diffusion Tensor Imaging in the Diagnosis of Prostate Cancer.

OBJECTIVE: The aim of this work was to demonstrate capabilities of diffusion tensor imaging as a diagnostic tool for prostate cancer in comparison with the apparent diffusion coefficient. METHODS: 364 patients with suspected prostate cancer underwent multiparametric magnetic resonance imaging including diffusion tensor imaging. RESULTS: The anatomical structure of the prostate obtained on T2-weighted imaging was compared with the apparent diffusion coefficient and diffusion tensor imaging maps. The rest of the gland (central and peripheral regions) were used as healthy areas. The apparent diffusion coefficient at diffusion-weighted imaging, fractional anisotropy and mean diffusivity at diffusion tensor imaging were evaluated in pathological zones. Cancer-suspicious areas of the prostate had high fractional anisotropy fractional anisotropy and low mean diffusivity compared to unaltered areas. Fractional anisotropy values were significantly elevated in central gland cancer, compared to normal tissue, and slightly elevated in peripheral zone cancer. CONCLUSION: Diffusion tensor imaging has the potential to identify prostate cancer with high accuracy and specificity. The combination of standard magnetic resonance imaging and diffusion tensor imaging can significantly improve the prognosis of the disease during active surveillance. The fractional anisotropy and mean diffusivity values can be useful in assessing the grade of malignancy and the radiolopathological correlation of the lesion.

Effects of Multimodal Physical Therapy on Pain, Disability, H-reflex, and Diffusion Tensor Imaging Parameters in Patients With Lumbosacral Radiculopathy Due to Lumbar Disc Herniation: A Preliminary Trial.

Background Lumbosacral radiculopathy (LSR) due to lumbar disc herniation (LDH) is a condition caused by mechanical compression of nerve roots. Various physical therapy interventions have been proposed for the conservative management of LSR due to LDH. However, the study of physical therapy interventions in a multimodal form is lacking. Additionally, the effect of physical therapy on diffusion tensor imaging (DTI) parameters of the compressed nerve root has not been studied. This study aimed to investigate the effects of multimodal physical therapy (MPT) on pain, disability, soleus H-reflex, and DTI parameters of the compressed nerve root in patients with chronic unilateral LSR due to LDH. Methods A prospective preliminary pre-post clinical trial with a convenience sample was conducted. A total of 14 patients with chronic unilateral LSR due to paracentral L4-L5 or L5-S1 LDH were recruited for the study. Participants received a total of 18 sessions of a six-week MPT program that consisted of electrophysical agents, manual therapy interventions, and core stability exercises. Electrophysical agents involved interferential current and hot pack. Manual therapy interventions included myofascial release, side posture positional distraction, passive spinal rotation mobilization, and high-velocity low-amplitude manipulation. Visual analog scale (VAS), Roland-Morris Disability Questionnaire (RMDQ), soleus H-reflex amplitude, side-to-side amplitude (H/H) ratio, fractional anisotropy (FA), and apparent diffusion coefficient (ADC) of the compressed nerve root were measured at baseline and post-intervention. Results There were significant improvements in VAS, RMDQ, H/H ratio, FA, and ADC of the compressed nerve root. Furthermore, significant improvement was found in the affected side compared with the contralateral side in H-reflex amplitude. Conclusions The observations of this preliminary trial suggest that MPT is a successful intervention in patients with chronic unilateral LSR due to LDH. Regarding DTI parameters of the compressed nerve root, FA increased and ADC decreased. Future studies with a control group, large sample sizes, and longer follow-up periods are needed.

Utility of Diffusion Tensor Imaging for Prognosis and Management of Cervical Spondylotic Myelopathy: A PRISMA Review.

OBJECTIVE: As advances are made in quantitative magnetic resonance imaging, specifically diffusion tensor imaging, researchers have investigated its potential to serve as a biomarker of disease or prognosticator for postoperative recovery in the management of cervical spondylotic myelopathy. Here, we narratively review the current state of the emerging literature, describing areas of consensus and disagreement. METHODS: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we queried 2 large databases for original manuscripts published in English and systematically produced a narrative review of the use of diffusion tensor imaging in the management of cervical spondylotic myelopathy. RESULTS: Of the 437 manuscripts initially returned in our query, 29 met the final inclusion criteria, and data were extracted regarding diffusion tensor imaging indices and their relationships with clinical outcomes following surgery. Preoperative fractional anisotropy was most commonly found to correlate closely with postsurgical clinical outcomes, though results were mixed. CONCLUSIONS: Preoperative fractional anisotropy most frequently and best correlates with functional outcomes following surgery for cervical spondylotic myelopathy, according to a review of the current literature. The findings were not universal and at times contradictory, highlighting the need for high-quality future investigations to better define the utility of diffusion tensor imaging in spinal disease.

Association among internalizing problems, white matter integrity, and social difficulties in children with autism spectrum disorder.

Autism spectrum disorder (ASD) is characterized by social difficulties and often accompanied by internalizing and externalizing problems, which are frequently overlooked. Here, we examined and compared fractional anisotropy (FA) between 79 children with ASD (aged 4-7.8 years) and 70 age-, gender-, and handedness- matched typically developing controls (TDCs, aged 3-7.2 years). We aimed to explore the relationship among social difficulties, internalizing and externalizing problems, and brain structural foundation (characterized by white matter integrity). Compared with the TDCs, the children with ASD exhibited more severe internalizing and externalizing problems, which were positively correlated with social difficulties. Reduced FA values were observed in specific white matter tracts that integrate a fronto-temporal-occipital circuit. In particular, the FA values within this circuit were negatively correlated with internalizing problems and SRS-TOTAL scores. Mediation analysis revealed that internalizing problems mediated the relationship between the FA values in the left middle longitudinal fasciculus (L-MdLF) and corpus callosum forceps major (CCM) and social difficulties in children with ASD. These findings contribute to our understanding of social difficulties, internalizing and externalizing problems, and white matter integrity in children with ASD and highlight internalizing problems as a mediator between social difficulties and white matter integrity.

Polygenic susceptibility for multiple sclerosis is associated with working memory in low-performing young adults.

BACKGROUND: Multiple sclerosis (MS) is a complex disease with substantial heritability estimates. Besides typical clinical manifestations such as motor and sensory deficits, MS is characterized by structural and functional brain abnormalities, and by cognitive impairment such as decreased working memory (WM) performance. OBJECTIVES: We investigated the possible link between the polygenic risk for MS and WM performance in healthy adults (18-35 years). Additionally, we addressed the relationship between polygenic risk for MS and white matter fractional anisotropy (FA). METHODS: We generated a polygenic risk score (PRS) of MS susceptibility and investigated its association with WM performance in 3282 healthy adults (two subsamples, N1 = 1803, N2 = 1479). The association between MS-PRS and FA was studied in the second subsample. MS severity PRS associations were also investigated for the WM and FA measurements. RESULTS: MS-PRS was significantly associated with WM performance within the 10% lowest WM-performing individuals (p = 0.001; pFDR = 0.018). It was not significantly associated with any of the investigated FA measurements. MS severity PRS was significantly associated with brain-wide mean FA (p = 0.041) and showed suggestive associations with additional FA measurements. CONCLUSIONS: By identifying a genetic link between MS and WM performance this study contributes to the understanding of the genetic complexity of MS, and hopefully to the possible identification of molecular pathways linked to cognitive deficits in MS. It also contributes to the understanding of genetic associations with MS severity, as these associations seem to involve distinct biological pathways compared to genetic variants linked to the overall risk of developing MS.

In vivo effect of LATE-NC on integrity of white matter connections to the hippocampus.

INTRODUCTION: TAR DNA-binding protein 43 (TDP-43) is a highly prevalent proteinopathy that is involved in neurodegenerative processes, including axonal damage. To date, no ante mortem biomarkers exist for TDP-43, and few studies have directly assessed its impact on neuroimaging measures utilizing pathologic quantification. METHODS: Ante mortem diffusion-weighted images were obtained from community-dwelling older adults. Regression models calculated the relationship between post mortem TDP-43 burden and ante mortem fractional anisotropy (FA) within each voxel in connection with the hippocampus, controlling for coexisting Alzheimer's disease and demographics. RESULTS: Results revealed a significant negative relationship (false discovery rate [FDR] corrected p < .05) between post mortem TDP-43 and ante mortem FA in one cluster within the left medial temporal lobe connecting to the parahippocampal cortex, entorhinal cortex, and cingulate, aligning with the ventral subdivision of the cingulum. FA within this cluster was associated with cognition. DISCUSSION: Greater TDP-43 burden is associated with lower FA within the limbic system, which may contribute to impairment in learning and memory. HIGHLIGHTS: Post mortem TDP-43 pathological burden is associated with reduced ante mortem fractional anisotropy. Reduced FA located in the parahippocampal portion of the cingulum. FA in this area was associated with reduced episodic and semantic memory. FA in this area was associated with increased inward hippocampal surface deformation.

Finding the limits of deep learning clinical sensitivity with fractional anisotropy (FA) microstructure maps.

Background: Quantitative maps obtained with diffusion weighted (DW) imaging, such as fractional anisotropy (FA) -calculated by fitting the diffusion tensor (DT) model to the data,-are very useful to study neurological diseases. To fit this map accurately, acquisition times of the order of several minutes are needed because many noncollinear DW volumes must be acquired to reduce directional biases. Deep learning (DL) can be used to reduce acquisition times by reducing the number of DW volumes. We already developed a DL network named "one-minute FA," which uses 10 DW volumes to obtain FA maps, maintaining the same characteristics and clinical sensitivity of the FA maps calculated with the standard method using more volumes. Recent publications have indicated that it is possible to train DL networks and obtain FA maps even with 4 DW input volumes, far less than the minimum number of directions for the mathematical estimation of the DT. Methods: Here we investigated the impact of reducing the number of DW input volumes to 4 or 7, and evaluated the performance and clinical sensitivity of the corresponding DL networks trained to calculate FA, while comparing results also with those using our one-minute FA. Each network training was performed on the human connectome project open-access dataset that has a high resolution and many DW volumes, used to fit a ground truth FA. To evaluate the generalizability of each network, they were tested on two external clinical datasets, not seen during training, and acquired on different scanners with different protocols, as previously done. Results: Using 4 or 7 DW volumes, it was possible to train DL networks to obtain FA maps with the same range of values as ground truth - map, only when using HCP test data; pathological sensitivity was lost when tested using the external clinical datasets: indeed in both cases, no consistent differences were found between patient groups. On the contrary, our "one-minute FA" did not suffer from the same problem. Conclusion: When developing DL networks for reduced acquisition times, the ability to generalize and to generate quantitative biomarkers that provide clinical sensitivity must be addressed.

Abnormal structure and function of white matter in obsessive-compulsive disorder.

BACKGROUND: Abnormal structure and function of gray matter (GM) have been discovered in the cortico-striatal-thalamic-cortical (CSTC) circuit in obsessive-compulsive disorder (OCD). The GM structure and function may be influenced by the structure and function of the white matter (WM). Therefore, it is crucial to explore the characteristics of WM in OCD. METHODS: Diffusion tensor imaging and resting-state functional magnetic resonance imaging data of 52 patients with OCD and 39 healthy controls (HCs) were collected. The tract-based spatial statistics, amplitude of low-frequency fluctuations (ALFF), and structural-functional coupling approaches were utilized to explore the WM structure and function. Furthermore, the relationship between the abnormal WM structure and function and clinical symptoms of OCD was investigated using Pearson's correlation. Support vector machine was performed to evaluate whether patients with OCD could be identified with the changed WM structure and function. RESULTS: Compared to HCs, the lower fractional anisotropy (FA) values of four clusters including the superior corona radiata, anterior corona radiata, right superior longitudinal fasciculus, corpus callosum, left posterior corona radiata, fornix, and the right anterior limb of internal capsule, reduced ALFF/FA ratio in the left anterior thalamic radiation (ATR), and the decreased functional connectivity between the left ATR and the left dorsal lateral prefrontal cortex within CSTC circuit at rest were observed in OCD. The decreased ALFF/FA ratio in the left ATR negatively correlated with Yale-Brown Obsessive-Compulsive Scale obsessive thinking scores and Hamilton Anxiety Rating Scale scores in OCD. Furthermore, the features that combined the abnormal WM structure and function performed best in distinguishing OCD from HCs with the appropriate accuracy (0.80), sensitivity (0.82), as well as specificity (0.80). CONCLUSION: Current research discovered changed WM structure and function in OCD. Furthermore, abnormal WM structural-functional coupling may lead to aberrant GM connectivity within the CSTC circuit at rest in OCD. TRIAL REGISTRATION: Study on the mechanism of brain network in obsessive-compulsive disorder with multi-model magnetic resonance imaging (ChiCTR-COC-17013301).

Presence of Auditory Pathway Abnormalities in Children With Neurofibromatosis Type 1 With Brainstem Focal Areas of Abnormal Signal Intensity: Diffusion Tensor Imaging Features.

Background: To investigate whether there is a difference in mean diffusivity (MD) and fractional anisotropy (FA) values in the auditory pathways of neurofibromatosis type 1 patients with and without focal areas of abnormal signal intensity (FASI) compared to healthy controls by using diffusion tensor imaging (DTI). Methods: Patients were classified as group 1 with focal areas of abnormal signal intensity in the brainstem, group 2 without focal areas of abnormal signal intensity, and healthy control group 3 according to the MRI findings. Mean diffusivity and fractional anisotropy values of lateral lemniscus, inferior colliculus, corpus geniculatum mediale, Heschl gyrus, and brainstem were compared between groups. The correlation between mean diffusivity and fractional anisotropy values of auditory pathways and age was investigated. Results: There was a significant difference between group 1 and group 2 in terms of mean diffusivity and fractional anisotropy values at lateral lemniscus, inferior colliculus, corpus geniculatum mediale, and Heschl gyrus. Increased mean diffusivity and decreased fractional anisotropy values at brainstem were found in group 1. There was a significant difference between group 1 and group 3 in terms of mean diffusivity values at all auditory pathways. Fractional anisotropy values obtained from lateral lemniscus, inferior colliculus, and Heschl gyrus decreased in group 1 compared with group 3. There was a negative correlation between mean diffusivity values and positive correlation between fractional anisotropy values at lateral lemniscus, inferior colliculus, Heschl gyrus, and age. Conclusions: Our diffusion tensor imaging findings show that the neuronal integrity of the auditory pathways is affected in neurofibromatosis type 1 patients with brainstem focal areas of abnormal signal intensity. We think that the disappearance of brainstem focal areas of abnormal signal intensity associated with myelin repair and the regression of diffusion tensor imaging changes in the auditory pathways occur simultaneously with advancing age in patients with neurofibromatosis type 1.

Dynamic functional connectivity is modulated by the amount of p-Tau231 in blood in cognitively intact participants.

INTRODUCTION: Electrophysiology and plasma biomarkers are early and non-invasive candidates for Alzheimer's disease detection. The purpose of this paper is to evaluate changes in dynamic functional connectivity measured with magnetoencephalography, associated with the plasma pathology marker p-tau231 in unimpaired adults. METHODS: 73 individuals were included. Static and dynamic functional connectivity were calculated using leakage corrected amplitude envelope correlation. Each source's strength entropy across trials was calculated. A data-driven statistical analysis was performed to find the association between functional connectivity and plasma p-tau231 levels. Regression models were used to assess the influence of other variables over the clusters' connectivity. RESULTS: Frontotemporal dynamic connectivity positively associated with p-tau231 levels. Linear regression models identified pathological, functional and structural factors that influence dynamic functional connectivity. DISCUSSION: These results expand previous literature on dynamic functional connectivity in healthy individuals at risk of AD, highlighting its usefulness as an early, non-invasive and more sensitive biomarker.

White Matter Microstructure Changes Revealed by Diffusion Kurtosis and Diffusion Tensor Imaging in Mutant Huntingtin Gene Carriers.

Background: Diffusion magnetic resonance imaging (dMRI) has revealed microstructural changes in white matter (WM) in Huntington's disease (HD). Objective: To compare the validities of different dMRI, i.e., diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) in HD. Methods: 22 mutant huntingtin (mHTT) carriers and 14 controls were enrolled. Clinical assessments and dMRI were conducted. Based on CAG-Age Product (CAP) score, mHTT carriers were categorized into high CAP (hCAP) and medium and low CAP (m& lCAP) groups. Spearman analyses were used to explore correlations between imaging parameters in brain regions and clinical assessments. Receiver operating characteristic (ROC) was used to distinguish mHTT carriers from control, and define the HD patients at advanced stage. Results: Compared to controls, mHTT carriers exhibited WM changes in DKI and DTI. There were 22 more regions showing significant differences in HD detected by MK than FA. Only MK in five brain regions showed significantly difference between any two group, and negatively correlated with the disease burden (r = -0.80 to -0.71). ROC analysis revealed that MK was more sensitive and FA was more specific, while Youden index showed that the integration of FA and MK gave rise to higher authenticities, in distinguishing m& lCAP from controls (Youden Index = 0.786), and discerning different phase of HD (Youden Index = 0.804). Conclusions: Microstructural changes in WM occur at early stage of HD and deteriorate over the disease progression. Integrating DKI and DTI would provide the best accuracies for differentiating early HD from control and identifying advanced HD.

Ultra-early navigated transcranial magnetic stimulation for perioperative stroke: anatomo-functional report.

Navigated repetitive transmagnetic stimulation is a non-invasive and safe brain activity modulation technique. When combined with the classical rehabilitation process in stroke patients it has the potential to enhance the overall neurologic recovery. We present a case of a peri-operative stroke, treated with ultra-early low frequency navigated repetitive transmagnetic stimulation over the contralesional hemisphere. The patient received low frequency navigated repetitive transmagnetic stimulation within 12 hours of stroke onset for seven consecutive days and a significant improvement in his right sided weakness was noticed and he was discharge with normal power. This was accompanied by an increase in the number of positive responses evoked by navigated repetitive transmagnetic stimulation and a decrease of the resting motor thresholds at a cortical level. Subcortically, a decrease in the radial, axial, and mean diffusivity were recorded in the ipsilateral corticospinal tract and an increase in fractional anisotropy, axial diffusivity, and mean diffusivity was observed in the interhemispheric fibers of the corpus callosum responsible for the interhemispheric connectivity between motor areas. Our case demonstrates clearly that ultra-early low frequency navigated repetitive transmagnetic stimulation applied to the contralateral motor cortex can lead to significant clinical motor improvement in patients with subcortical stroke.

Structural white matter abnormalities in Schizophrenia and associations with neurocognitive performance and symptom severity.

Schizophrenia is associated with robust white matter (WM) abnormalities but influences of potentially confounding variables and relationships with cognitive performance and symptom severity remain to be fully determined. This study was designed to evaluate WM abnormalities based on diffusion tensor imaging (DTI) in individuals with schizophrenia, and their relationships with cognitive performance and symptom severity. Data from individuals with schizophrenia (SZ; n=138, mean age±SD=39.02±11.82; 105 males) and healthy controls (HC; n=143, mean age±SD=37.07±10.84; 102 males) were collected as part of the Function Biomedical Informatics Research Network Phase 3 study. Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) were compared between individuals with schizophrenia and healthy controls, and their relationships with neurocognitive performance and symptomatology assessed. Individuals with SZ had significantly lower FA in forceps minor and the left inferior fronto-occipital fasciculus compared to HC. FA in several tracts were associated with speed of processing and attention/vigilance and the severity of the negative symptom alogia. This study suggests that regional WM abnormalities are fundamentally involved in the pathophysiology of schizophrenia and may contribute to cognitive performance deficits and symptom expression observed in schizophrenia.

Diffusion Tensor Imaging Identifies Cervical Spondylosis, Myelitis, and Spinal Cord Tumors.

BACKGROUND: Diffusion tensor imaging (DTI) has been increasingly recognized for its capability to study microstructural changes in the neuropathology of brain diseases. However, the optimal DTI metric and its diagnostic utility for a variety of spinal cord diseases are still under investigation. PURPOSE: To evaluate the diagnostic efficacy of DTI metrics for differentiating between cervical spondylosis, myelitis, and spinal tumors. METHODS: This retrospective study analyzed DTI scans from 68 patients (22 with cervical spondylosis, 23 with myelitis, and 23 with spinal tumors). DTI indicators, including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD), were calculated. The Kruskal-Wallis test was used to compare these indicators, followed by Receiver Operating Characteristic (ROC) curve analysis, to evaluate the diagnostic efficacy of each indicator across disease pairs. Additionally, we explored the correlations of DTI indicators with specific clinical measurements. RESULTS: FA values were significantly lower in tumor patients compared to those with cervical spondylosis (p < 0.0001) and myelitis (p < 0.05). Additionally, tumor patients exhibited significantly elevated MD and RD values relative to the spondylosis and myelitis groups. ROC curve analysis underscored FA's superior discriminative performance, with an area under the curve (AUC) of 0.902 for differentiating tumors from cervical spondylosis, and an AUC of 0.748 for distinguishing cervical myelitis from spondylosis. Furthermore, a significant negative correlation was observed between FA values and Expanded Disability Status Scores (EDSSs) in myelitis patients (r = -0.62, p = 0.002), as well as between FA values and Ki-67 scores in tumor patients (r = -0.71, p = 0.0002). CONCLUSION: DTI indicators, especially FA, have the potential in distinguishing spondylosis, myelitis, and spinal cord tumors. The significant correlation between FA values and clinical indicators highlights the value of FA in the clinical assessment and prognosis of spinal diseases and may be applied in diagnostic protocols in the future.