Search

•Thalamic tissue damage in multiple sclerosis (MS) exhibits a distinct gradient from the ventricular surface.•Quantitative gradient-recalled echo (qGRE) MRI analysis reveals a steeper periventricular thalamic gradient of tissue integrity in MS patients compared to healthy controls.•Increased thalamic gradient correlates with longer disease duration and higher expanded disability status scale (EDSS) scores, suggesting a link between periventricular thalamic gradient and clinical disability in MS.

Clinical diagnosis often focuses on identifying the single cause of a patient’s symptoms but it is becoming increasingly recognized that a subset of patients exist where 2 pathological entities coexist. These patients present a particular diagnostic challenge because the first “positive” diagnostic test is not the definitive stopping point in their evaluation. Here, we present the case of a 47-year-old woman with multiple cranial neuropathies and a polyradiculopathy. A significant pleocytosis in the cerebrospinal fluid sparked a broad evaluation which revealed pathologic evidence of sarcoidosis and molecular evidence of neurofascin (NF)-155 and NF-140 antibodies. The pathogenic contribution of these 2 pathologic entities, or interaction, to this patient’s case is not clear. Nevertheless, the patient responded robustly to steroids and symptoms significantly improved. This case is a demonstration of the balance between Occam’s razor and Hickam’s dictum in clinical practice.

•This study used the R2t* measure to quantify tissue damage in lesions and non-lesional tissue in MS and MOGAD•Abnormalities in non-lesional tissue are present in MOGAD but are of modest magnitude compared to MS•WML damage in MOGAD lesions is less severe compared to MS•Overall, MOGAD was associated with less tissue damage compared to MS

Determine whether HIV and combination antiretroviral therapy (cART) affect resting-state functional connectivity (rs-fc) between the striatum and the cortical regions.

IMPORTANCE: Autosomal dominant Alzheimer disease (ADAD) is caused by rare genetic mutations in 3 specific genes in contrast to late-onset Alzheimer disease (LOAD), which has a more polygenetic risk profile. OBJECTIVE: To assess the similarities and differences in functional connectivity changes owing to ADAD and LOAD. DESIGN, SETTING, AND PARTICIPANTS: We analyzed functional connectivity in multiple brain resting state networks (RSNs) in a cross-sectional cohort of participants with ADAD (n = 79) and LOAD (n = 444), using resting-state functional connectivity magnetic resonance imaging at multiple international academic sites. MAIN OUTCOMES AND MEASURES: For both types of AD, we quantified and compared functional connectivity changes in RSNs as a function of dementia severity measured by the Clinical Dementia Rating Scale. In ADAD, we qualitatively investigated functional connectivity changes with respect to estimated years from onset of symptoms within 5 RSNs. RESULTS: A decrease in functional connectivity with increasing Clinical Dementia Rating scores were similar for both LOAD and ADAD in multiple RSNs. Ordinal logistic regression models constructed in one type of Alzheimer disease accurately predicted clinical dementia rating scores in the other, further demonstrating the similarity of functional connectivity loss in each disease type. Among participants with ADAD, functional connectivity in multiple RSNs appeared qualitatively lower in asymptomatic mutation carriers near their anticipated age of symptom onset compared with asymptomatic mutation noncarriers. CONCLUSIONS AND RELEVANCE: Resting-state functional connectivity magnetic resonance imaging changes with progressing AD severity are similar between ADAD and LOAD. Resting-state functional connectivity magnetic resonance imaging may be a useful end point for LOAD and ADAD therapy trials. Moreover, the disease process of ADAD may be an effective model for the LOAD disease process.

AbstractMuch effort in recent years has focused on understanding the effects of Alzheimer's disease (AD) on neural function. This effort has resulted in an enormous number of papers describing different facets of the functional derangement seen in AD. A particularly important tool for these investigations has been resting-state functional connectivity. Attempts to comprehensively synthesize resting-state functional connectivity results have focused on the potential utility of functional connectivity as a biomarker for disease risk, disease staging, or prognosis. While these are all appropriate uses of this technique, the purpose of this review is to examine how functional connectivity disruptions inform our understanding of AD pathophysiology. Here, we examine the rationale and methodological considerations behind functional connectivity studies and then provide a critical review of the existing literature. In conclusion, we propose a hypothesis regarding the development and spread of functional connectivity deficits seen in AD.

The present study examined functional MRI (fMRI) BOLD signal changes in response to object categorization during response selection and inhibition. Young adults (N=16) completed a GoNoGo task with varying object categorization requirements while fMRI data were recorded. Response inhibition elicited increased signal change in various brain regions, including medial frontal areas, compared with response selection. BOLD signal in an area within the right angular gyrus was increased when higher-order categorization was mandated. In addition, signal change during response inhibition varied with categorization requirements in the left inferior temporal gyrus (lIT). lIT-mediated response inhibition when inhibiting the response only required lower-order categorization, but lIT mediated both response selection and inhibition when selecting and inhibiting the response required higher-order categorization. The findings characterized mechanisms mediating response inhibition associated with semantic object categorization in the ‘what’ visual object memory system.

IMPORTANCE Resting-state functional connectivity magnetic resonance imaging has great potential for characterizing pathophysiological changes during the preclinical phase of Alzheimer disease. OBJECTIVE To assess the relationship between default mode network integrity and cerebrospinal fluid biomarkers of Alzheimer disease pathology in cognitively normal older individuals. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional cohort study at The Charles F. and Joanne Knight Alzheimer’s Disease Research Center at Washington University in St Louis, St Louis, Missouri, among 207 older adults with normal cognition (Clinical Dementia Rating, 0). MAIN OUTCOMES AND MEASURES Resting-state functional connectivity magnetic resonance imaging measures of default mode network integrity. RESULTS Decreased cerebrospinal fluid Aβ42 and increased cerebrospinal fluid phosphorylated tau181 were independently associated with reduced default mode network integrity, with the most prominent decreases in functional connectivity observed between the posterior cingulate and medial temporal regions. Observed reductions in functional connectivity were unattributable to age or structural atrophy in the posterior cingulate and medial temporal areas. Similar resting-state functional connectivity magnetic resonance imaging findings in relation to cerebrospinal fluid biomarkers were obtained using region-of-interest analyses and voxelwise correlation mapping. CONCLUSIONS AND RELEVANCE Both Aβ and tau pathology affect default mode network integrity before clinical onset of Alzheimer disease.

Resting-state functional connectivity MRI (rs-fcMRI) may provide insight into the neurophysiology of HIV and aging.

PET imaging of pathological tau correlates more closely with Alzheimer’s disease–related cognitive impairment than does imaging of β-amyloid.