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Heliyon May 2024Hippocampus is the most widely studied brain area coupled with impairment of memory in a variety of neurological diseases and Alzheimer's disease (AD). The limbic... (Review)
Review
Hippocampus is the most widely studied brain area coupled with impairment of memory in a variety of neurological diseases and Alzheimer's disease (AD). The limbic structures within the Papez circuit have been linked to various aspects of cognition. Unfortunately, the brain regions that include this memory circuit are often ignored in terms of understanding cognitive decline in these diseases. To properly comprehend where cognition problems originate, it is crucial to clarify any aberrant contributions from all components of a specific circuit -on both a local and a global level. The pharmacological treatments currently available are not long lasting. Deep Brain Stimulation (DBS) emerged as a new powerful therapeutic approach for alleviation of the cognitive dysfunctions. Metabolic, functional, electrophysiological, and imaging studies helped to find out the crucial nodes that can be accessible for DBS. Targeting these nodes within the memory circuit produced significant improvement in learning and memory by disrupting abnormal circuit activity and restoring the physiological network. Here, we provide an overview of the neuroanatomy of the circuit of Papez along with the mechanisms and various deep brain stimulation targets of the circuit structures which could be significant for improving cognitive dysfunctions in AD.
PubMed: 38726200
DOI: 10.1016/j.heliyon.2024.e30574 -
Annals of Translational Medicine Apr 2024Interstitial cystitis/bladder pain syndrome (IC/BPS) is defined as chronic pelvic pain plus a bladder symptom, usually urge. Evidence is offered to show IC/BPS forms... (Review)
Review
Interstitial cystitis/bladder pain syndrome (IC/BPS) is defined as chronic pelvic pain plus a bladder symptom, usually urge. Evidence is offered to show IC/BPS forms part of the posterior fornix syndrome (PFS), which was defined in 1993 as: chronic pelvic pain (CPP), urge, frequency, nocturia, abnormal emptying, post-void residual urine, caused by uterosacral ligament (USL) laxity and cured or improved by USL repair. The IC/BPS definition implies that the urge and pain of IC/BPS is from a single (as yet unknown) pathogenic origin. However, when urge and pain are viewed from the perspective of the PFS, though both have the same lax USL origin, the anatomical pathway from lax USL to symptom manifestation is very different manifestation. For CPP the anatomical pathway is the inability of loose USLs to support pelvic visceral plexuses (VPs); it is hypothesized that inability of weak USLs to mechanically supports VPs, the afferent nerve synapse from end organs may fire off autologous afferent impulses to the brain which interprets them as pain from end organs such as urothelium, vulva, lower abdomen. For urge, the anatomical pathway is very different: lax USLs weaken the directional pelvic muscle forces which stretch the vagina to support the urothelial stretch receptors. The receptors fire off afferent impulses to the cortex at a lower bladder volume, and these are interpreted as "urge to go". Mechanical support of USLs relieves both pain and urge, as does USL repair.
PubMed: 38721463
DOI: 10.21037/atm-23-1865 -
Human Brain Mapping May 2024The global ageing of populations calls for effective, ecologically valid methods to support brain health across adult life. Previous evidence suggests that music can...
The global ageing of populations calls for effective, ecologically valid methods to support brain health across adult life. Previous evidence suggests that music can promote white matter (WM) microstructure and grey matter (GM) volume while supporting auditory and cognitive functioning and emotional well-being as well as counteracting age-related cognitive decline. Adding a social component to music training, choir singing is a popular leisure activity among older adults, but a systematic account of its potential to support healthy brain structure, especially with regard to ageing, is currently missing. The present study used quantitative anisotropy (QA)-based diffusion MRI connectometry and voxel-based morphometry to explore the relationship of lifetime choir singing experience and brain structure at the whole-brain level. Cross-sectional multiple regression analyses were carried out in a large, balanced sample (N = 95; age range 21-88) of healthy adults with varying levels of choir singing experience across the whole age range and within subgroups defined by age (young, middle-aged, and older adults). Independent of age, choir singing experience was associated with extensive increases in WM QA in commissural, association, and projection tracts across the brain. Corroborating previous work, these overlapped with language and limbic networks. Enhanced corpus callosum microstructure was associated with choir singing experience across all subgroups. In addition, choir singing experience was selectively associated with enhanced QA in the fornix in older participants. No associations between GM volume and choir singing were found. The present study offers the first systematic account of amateur-level choir singing on brain structure. While no evidence for counteracting GM atrophy was found, the present evidence of enhanced structural connectivity coheres well with age-typical structural changes. Corroborating previous behavioural studies, the present results suggest that regular choir singing holds great promise for supporting brain health across the adult life span.
Topics: Humans; Adult; Male; Middle Aged; Aged; Female; Young Adult; Singing; Aged, 80 and over; White Matter; Aging; Cross-Sectional Studies; Brain; Gray Matter; Diffusion Magnetic Resonance Imaging; Diffusion Tensor Imaging
PubMed: 38716698
DOI: 10.1002/hbm.26705 -
Cureus Apr 2024Background The aim of this study is to evaluate the clinical and radiological findings of metastatic tumors and primary brain tumors affecting the fornix. Methods ...
Background The aim of this study is to evaluate the clinical and radiological findings of metastatic tumors and primary brain tumors affecting the fornix. Methods Between January 2015 and March 2023, we retrospectively evaluated 1087 patients of both sexes who underwent cranial magnetic resonance imaging (MRI) for a preliminary diagnosis of intracranial malignancy in the radiology department of our hospital. Two radiologists with six and 10 years of experience in MRI examination assessed the relationship between primary and metastatic tumors and the fornix. Results Involvement of the fornix was diagnosed in 29 of the 1087 patients (2.66%), of which fornix was affected by metastatic lesions in 14 patients (48.2%) and primary tumors in 15 patients (51.7%). The majority of metastatic lesions were from lung and breast cancers, with other tumor types including osteosarcoma, renal cell carcinoma, pancreatic adenocarcinoma, pleomorphic sarcoma, and diffuse large B-cell lymphoma. Among all primary tumors, glioblastoma was the most common primary brain tumor invading the fornix, with other diagnoses including diffuse astrocytoma, medulloblastoma, and anaplastic oligodendroglioma. Metastatic and primary brain tumors affecting the fornix were detected over a broad timeline, from the time of diagnosis up to 120 months after diagnosis. A retrospective evaluation of medical records revealed memory deficits in four patients. Conclusion The fornix can be affected by both metastatic and primary brain tumors. It is crucial to understand the relevant neuroanatomical relationships when evaluating lesions that affect the fornix.
PubMed: 38689678
DOI: 10.7759/cureus.57612 -
JAMA Network Open Apr 2024Mild traumatic brain injury (mTBI) is the signature injury experienced by military service members and is associated with poor neuropsychiatric outcomes. Yet, there is a...
IMPORTANCE
Mild traumatic brain injury (mTBI) is the signature injury experienced by military service members and is associated with poor neuropsychiatric outcomes. Yet, there is a lack of reliable clinical tools for mTBI diagnosis and prognosis.
OBJECTIVE
To examine the white matter microstructure and neuropsychiatric outcomes of service members with a remote history of mTBI (ie, mTBI that occurred over 2 years ago) using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI).
DESIGN, SETTING, AND PARTICIPANTS
This case-control study examined 98 male service members enrolled in a study at the National Intrepid Center of Excellence. Eligible participants were active duty status or able to enroll in the Defense Enrollment Eligibility Reporting system, ages 18 to 60 years, and had a remote history of mTBI; controls were matched by age.
EXPOSURES
Remote history of mTBI.
MAIN OUTCOMES AND MEASURES
White matter microstructure was assessed using a region-of-interest approach of skeletonized diffusion images, including DTI (fractional anisotropy, mean diffusivity, radial diffusivity and axial diffusivity) and NODDI (orientation dispersion index [ODI], isotropic volume fraction, intra-cellular volume fraction). Neuropsychiatric outcomes associated with posttraumatic stress disorder (PTSD) and postconcussion syndrome were assessed.
RESULTS
A total of 65 male patients with a remote history of mTBI (mean [SD] age, 40.5 [5.0] years) and 33 age-matched male controls (mean [SD] age, 38.9 [5.6] years) were included in analysis. Compared with the control cohort, the 65 service members with mTBI presented with significantly more severe PTSD-like symptoms (mean [SD] PTSD CheckList-Civilian [PCL-C] version scores: control, 19.0 [3.8] vs mTBI, 41.2 [11.6]; P < .001). DTI and NODDI metrics were altered in the mTBI group compared with the control, including intra-cellular volume fraction of the right cortico-spinal tract (β = -0.029, Cohen d = 0.66; P < .001), ODI of the left posterior thalamic radiation (β = -0.006, Cohen d = 0.55; P < .001), and ODI of the left uncinate fasciculus (β = 0.013, Cohen d = 0.61; P < .001). In service members with mTBI, fractional anisotropy of the left uncinate fasciculus was associated with postconcussion syndrome (β = 5.4 × 10-3; P = .003), isotropic volume fraction of the genu of the corpus callosum with PCL-C (β = 4.3 × 10-4; P = .01), and ODI of the left fornix and stria terminalis with PCL-C avoidance scores (β = 1.2 × 10-3; P = .02).
CONCLUSIONS AND RELEVANCE
In this case-control study of military-related mTBI, the results suggest that advanced magnetic resonance imaging techniques using NODDI can reveal white matter microstructural alterations associated with neuropsychiatric symptoms in the chronic phase of mTBI. Diffusion trends observed throughout widespread white matter regions-of-interest may reflect mechanisms of neurodegeneration as well as postinjury tissue scarring and reorganization.
Topics: Humans; Male; Adult; Child, Preschool; Brain Concussion; Diffusion Tensor Imaging; Case-Control Studies; Military Personnel; White Matter; Post-Concussion Syndrome
PubMed: 38635266
DOI: 10.1001/jamanetworkopen.2024.8121 -
Scientific Reports Mar 2024Loss of myelin in the brain may lead to cognitive decline in Alzheimer's disease (AD). The ratio of T1 weighted/T2 weighted (T1w/T2w) on magnetic resonance imaging has...
Loss of myelin in the brain may lead to cognitive decline in Alzheimer's disease (AD). The ratio of T1 weighted/T2 weighted (T1w/T2w) on magnetic resonance imaging has been used as a proxy for myelin content in the brain. Using this approach, we investigated the correlation between the white matter (WM) T1w/T2w ratio and both cognitive scores and disease progression in AD. A total of 93 participants who were cognitively unimpaired or diagnosed with mild cognitive impairment or AD dementia were recruited between March 2021 and November 2022. All participants were assessed using neuropsychological tests, and a subset of the participants was assessed every 1 year to monitor disease progression. We observed significant positive associations between the WM T1w/T2w ratio and executive function within the fornix, sagittal stratum, anterior internal capsule, and body of the corpus callosum (False discovery rate [FDR]-corrected P-value < 0.05). There was a marginal interaction between the WM T1w/T2w ratio of the left anterior internal capsule and the longitudinal change in sum of boxes of the Clinical Dementia Rating Scale (FDR-corrected P-value = 0.05). The present study demonstrated that the WM T1w/T2w ratio was associated with executive function and disease progression, suggesting that it may be a novel neuroimaging marker for AD.
Topics: Humans; White Matter; Alzheimer Disease; Brain; Magnetic Resonance Imaging; Cognition; Cognitive Dysfunction; Myelin Sheath; Disease Progression
PubMed: 38538679
DOI: 10.1038/s41598-024-57287-5 -
ELife Mar 2024Storing and accessing memories is required to successfully perform day-to-day tasks, for example for engaging in a meaningful conversation. Previous studies in both...
Storing and accessing memories is required to successfully perform day-to-day tasks, for example for engaging in a meaningful conversation. Previous studies in both rodents and primates have correlated hippocampal cellular activity with behavioral expression of memory. A key role has been attributed to awake hippocampal replay - a sequential reactivation of neurons representing a trajectory through space. However, it is unclear if awake replay impacts immediate future behavior, gradually creates and stabilizes long-term memories over a long period of time (hours and longer), or enables the temporary memorization of relevant events at an intermediate time scale (seconds to minutes). In this study, we aimed to address the uncertainty around the timeframe of impact of awake replay by collecting causal evidence from behaving rats. We detected and disrupted sharp wave ripples (SWRs) - signatures of putative replay events - using electrical stimulation of the ventral hippocampal commissure in rats that were trained on three different spatial memory tasks. In each task, rats were required to memorize a new set of locations in each trial or each daily session. Interestingly, the rats performed equally well with or without SWR disruptions. These data suggest that awake SWRs - and potentially replay - does not affect the immediate behavior nor the temporary memorization of relevant events at a short timescale that are required to successfully perform the spatial tasks. Based on these results, we hypothesize that the impact of awake replay on memory and behavior is long-term and cumulative over time.
Topics: Rats; Animals; Spatial Memory; Wakefulness; Hippocampus; Neurons; Fornix, Brain
PubMed: 38530125
DOI: 10.7554/eLife.84004 -
Magnetic Resonance Imaging Jun 2024A substantial fraction of those who had Alzheimer's Disease (AD) pathology on autopsy did not have dementia in life. While biomarkers for AD pathology are...
BACKGROUND AND PURPOSE
A substantial fraction of those who had Alzheimer's Disease (AD) pathology on autopsy did not have dementia in life. While biomarkers for AD pathology are well-developed, biomarkers specific to cognitive domains affected by early AD are lagging. Diffusion MRI (dMRI) of the fornix is a candidate biomarker for early AD-related cognitive changes but is susceptible to bias due to partial volume averaging (PVA) with cerebrospinal fluid. The purpose of this work is to leverage multi-shell dMRI to correct for PVA and to evaluate PVA-corrected dMRI measures in fornix as a biomarker for cognition in AD.
METHODS
Thirty-three participants in the Cleveland Alzheimer's Disease Research Center (CADRC) (19 with normal cognition (NC), 10 with mild cognitive impairment (MCI), 4 with dementia due to AD) were enrolled in this study. Multi-shell dMRI was acquired, and voxelwise fits were performed with two models: 1) diffusion tensor imaging (DTI) that was corrected for PVA and 2) neurite orientation dispersion and density imaging (NODDI). Values of tissue integrity in fornix were correlated with neuropsychological scores taken from the Uniform Data Set (UDS), including the UDS Global Composite 5 score (UDSGC5).
RESULTS
Statistically significant correlations were found between the UDSGC5 and PVA-corrected measure of mean diffusivity (MDc, r = -0.35, p < 0.05) from DTI and the intracelluar volume fraction (ficvf, r = 0.37, p < 0.04) from NODDI. A sensitivity analysis showed that the relationship to MDc was driven by episodic memory, which is often affected early in AD, and language.
CONCLUSION
This cross-sectional study suggests that multi-shell dMRI of the fornix that has been corrected for PVA is a potential biomarker for early cognitive domain changes in AD. A longitudinal study will be necessary to determine if the imaging measure can predict cognitive decline.
Topics: Humans; Alzheimer Disease; Diffusion Tensor Imaging; Longitudinal Studies; Cross-Sectional Studies; Cognition; Diffusion Magnetic Resonance Imaging; Cognitive Dysfunction; Biomarkers
PubMed: 38521367
DOI: 10.1016/j.mri.2024.03.030 -
Frontiers in Endocrinology 2024This study aimed to identify disruptions in white matter integrity in type 2 diabetes mellitus (T2DM) patients by utilizing the white matter tract integrity (WMTI)...
Analysis of white matter tract integrity using diffusion kurtosis imaging reveals the correlation of white matter microstructural abnormalities with cognitive impairment in type 2 diabetes mellitus.
BACKGROUND
This study aimed to identify disruptions in white matter integrity in type 2 diabetes mellitus (T2DM) patients by utilizing the white matter tract integrity (WMTI) model, which describes compartment-specific diffusivities in the intra- and extra-axonal spaces, and to investigate the relationship between WMTI metrics and clinical and cognitive measurements.
METHODS
A total of 73 patients with T2DM and 57 healthy controls (HCs) matched for age, sex, and education level were enrolled and underwent diffusional kurtosis imaging and cognitive assessments. Tract-based spatial statistics (TBSS) and atlas-based region of interest (ROI) analysis were performed to compare group differences in diffusional metrics, including fractional anisotropy (FA), mean diffusivity (MD), axonal water fraction (AWF), intra-axonal diffusivity (D), axial extra-axonal space diffusivity (D), and radial extra-axonal space diffusivity (D) in multiple white matter (WM) regions. Relationships between diffusional metrics and clinical and cognitive functions were characterized.
RESULTS
In the TBSS analysis, the T2DM group exhibited decreased FA and AWF and increased MD, D, and D in widespread WM regions in comparison with the HC group, which involved 56.28%, 32.07%, 73.77%, 50.47%, and 75.96% of the mean WM skeleton, respectively ( < 0.05, TFCE-corrected). D detected most of the WM changes, which were mainly located in the corpus callosum, internal capsule, external capsule, corona radiata, posterior thalamic radiations, sagittal stratum, cingulum (cingulate gyrus), fornix (stria terminalis), superior longitudinal fasciculus, and uniform fasciculus. Additionally, D in the genu of the corpus callosum was significantly correlated with worse performance in TMT-A (β = 0.433, < 0.001) and a longer disease duration (β = 0.438, < 0.001).
CONCLUSIONS
WMTI is more sensitive than diffusion tensor imaging in detecting T2DM-related WM microstructure abnormalities and can provide novel insights into the possible pathological changes underlying WM degeneration in T2DM. D could be a potential imaging marker in monitoring disease progression in the brain and early intervention treatment for the cognitive impairment in T2DM.
Topics: Humans; White Matter; Diffusion Tensor Imaging; Diabetes Mellitus, Type 2; Diffusion Magnetic Resonance Imaging; Cognitive Dysfunction
PubMed: 38487342
DOI: 10.3389/fendo.2024.1327339 -
NeuroImage Apr 2024Posterior cortical atrophy (PCA) and dementia with Lewy bodies (DLB) show distinct atrophy and overlapping hypometabolism profiles, but it is unknown how disruptions in...
Posterior cortical atrophy (PCA) and dementia with Lewy bodies (DLB) show distinct atrophy and overlapping hypometabolism profiles, but it is unknown how disruptions in structural and functional connectivity compare between these disorders and whether breakdowns in connectivity relate to either atrophy or hypometabolism. Thirty amyloid-positive PCA patients, 24 amyloid-negative DLB patients and 30 amyloid-negative cognitively unimpaired (CU) healthy individuals were recruited at Mayo Clinic, Rochester, MN, and underwent a 3T head MRI, including structural MRI, resting state functional MRI (rsfMRI) and diffusion tensor imaging (DTI) sequences, as well as [F] fluorodeoxyglucose (FDG) PET. We assessed functional connectivity within and between 12 brain networks using rsfMRI and the CONN functional connectivity toolbox and calculated regional DTI metrics using the Johns Hopkins atlas. Multivariate linear-regression models corrected for multiple comparisons and adjusted for age and sex compared DTI metrics and within-network and between-network functional connectivity across groups. Regional gray-matter volumes and FDG-PET standard uptake value ratios (SUVRs) were calculated and analyzed at the voxel-level using SPM12. We used univariate linear-regression models to investigate the relationship between connectivity measures, gray-matter volume, and FDG-PET SUVR. On DTI, PCA showed degeneration in occipito-parietal white matter, posterior thalamic radiations, splenium of the corpus collosum and sagittal stratum compared to DLB and CU, with greater degeneration in the temporal white matter and the fornix compared to CU. We observed no white-matter degeneration in DLB compared to CU. On rsfMRI, reduced within-network connectivity was present in dorsal and ventral default mode networks (DMN) and the dorsal-attention network in PCA compared to DLB and CU, with reduced within-network connectivity in the visual and sensorimotor networks compared to CU. DLB showed reduced connectivity in the cerebellar network compared to CU. Between-network analysis showed increased connectivity in both cerebellar-to-sensorimotor and cerebellar-to-dorsal attention network connectivity in PCA and DLB. PCA showed reduced anterior DMN-to-cerebellar and dorsal attention-to-sensorimotor connectivity, while DLB showed reduced posterior DMN-to-sensorimotor connectivity compared to CU. PCA showed reduced dorsal DMN-to-visual connectivity compared to DLB. The multimodal analysis revealed weak associations between functional connectivity and volume in PCA, and between functional connectivity and metabolism in DLB. These findings suggest that PCA and DLB have unique connectivity alterations, with PCA showing more widespread disruptions in both structural and functional connectivity; yet some overlap was observed with both disorders showing increased connectivity from the cerebellum.
Topics: Humans; Lewy Body Disease; Diffusion Tensor Imaging; Fluorodeoxyglucose F18; Magnetic Resonance Imaging; Atrophy; Alzheimer Disease
PubMed: 38442778
DOI: 10.1016/j.neuroimage.2024.120564