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Working memory and episodic memory are two different processes, although the nature of their interrelationship is debated. As these processes are predominantly studied in isolation, it is unclear whether they crucially rely on different neural substrates. To obtain more insight in this, 81 adults with sub-acute ischemic stroke and 29 elderly controls were assessed on a visual working memory task, followed by a surprise subsequent memory test for the same stimuli. Multivariate, atlas- and track-based lesion-symptom mapping (LSM) analyses were performed to identify anatomical correlates of visual memory. Behavioral results gave moderate evidence for independence between discriminability in working memory and subsequent memory, and strong evidence for a correlation in response bias on the two tasks in stroke patients. LSM analyses suggested there might be independent regions associated with working memory and episodic memory. Lesions in the right arcuate fasciculus were more strongly associated with discriminability in working memory than in subsequent memory, while lesions in the frontal operculum in the right hemisphere were more strongly associated with criterion setting in subsequent memory. These findings support the view that some processes involved in working memory and episodic memory rely on separate mechanisms, while acknowledging that there might also be shared processes. [ABSTRACT FROM AUTHOR]

Introduction: Radiological thrombus characteristics are associated with patient outcomes and treatment success after acute ischemic stroke. These characteristics could be expected to undergo time-dependent changes due to factors influencing thrombus architecture like blood stasis, clot contraction, and natural thrombolysis. We investigated whether stroke onset-to-imaging time was associated with thrombus length, perviousness, and density in the MR CLEAN Registry population. Methods: We included 245 patients with M1-segment occlusions and thin-slice baseline CT imaging from the MR CLEAN Registry, a nation-wide multicenter registry of patients who underwent endovascular treatment for acute ischemic stroke within 6.5 h of onset in the Netherlands. We used multivariable linear regression to investigate the effect of stroke onset-to-imaging time (per 5 min) on thrombus length (in mm), perviousness and density (both in Hounsfield Units). In the first model, we adjusted for age, sex, intravenous thrombolysis, antiplatelet use, and history of atrial fibrillation. In a second model, we additionally adjusted for observed vs. non-observed stroke onset, CT-angiography collateral score, direct presentation at a thrombectomy-capable center vs. transfer, and stroke etiology. We performed exploratory subgroup analyses for intravenous thrombolysis administration, observed vs. non-observed stroke onset, direct presentation vs. transfer, and stroke etiology. Results: Median stroke onset-to-imaging time was 83 (interquartile range 53–141) min. Onset to imaging time was not associated with thrombus length nor perviousness (β 0.002; 95% CI −0.004 to 0.007 and β −0.002; 95% CI −0.015 to 0.011 per 5 min, respectively) and was weakly associated with thrombus density in the fully adjusted model (adjusted β 0.100; 95% CI 0.005–0.196 HU per 5 min). The subgroup analyses showed no heterogeneity of these findings in any of the subgroups, except for a significantly positive relation between onset-to-imaging time and thrombus density in patients transferred from a primary stroke center (adjusted β 0.18; 95% CI 0.022–0.35). Conclusion: In our population of acute ischemic stroke patients, we found no clear association between onset-to-imaging time and radiological thrombus characteristics. This suggests that elapsed time from stroke onset plays a limited role in the interpretation of radiological thrombus characteristics and their effect on treatment results, at least in the early time window. [ABSTRACT FROM AUTHOR]

Quantitative magnetic resonance imaging generates images of meaningful physical or chemical variables measured in physical units that allow quantitative comparisons between tissue regions and among subjects scanned at the same or different sites. Here, we show that we can acquire quantitative T1, T2*, and quantitative susceptibility mapping (QSM) information in a single acquisition, using a multi‐echo (ME) extension of the second gradient‐echo image of the MP2RAGE sequence. This combination is called MP2RAGE ME, or MP2RAGEME. The simultaneous acquisition results in large time savings, perfectly coregistered data, and minimal image quality differences compared to separately acquired data. Following a correction for residual transmit B1+‐sensitivity, quantitative T1, T2*, and QSM values were in excellent agreement with those obtained from separately acquired, also B1+‐corrected, MP2RAGE data and ME gradient echo data. The quantitative values from reference regions of interests were also in very good correspondence with literature values. From the MP2RAGEME data, we further derived a multiparametric cortical parcellation, as well as a combined arterial and venous map. In sum, our MP2RAGEME sequence has the benefit in large time savings, perfectly coregistered data and minor image quality differences. [ABSTRACT FROM AUTHOR]

Background. Despite successful antiretroviral therapy, people living with human immunodeficiency virus (PLWH) experience higher rates of age-related morbidity, including abnormal brain structure, brain function, and cognitive impairment. This has raised concerns that PLWH may experience accelerated aging-related brain pathology. Methods. We performed a multicenter longitudinal study of 134 virologically suppressed PLWH (median age, 56.0 years) and 79 demographically similar human immunodeficiency virus (HlV)-negative controls (median age, 57.2 years). To measure cognitive performance and brain pathology, we conducted detailed neuropsychological assessments and multimodality neuroimaging (T1-weighted, T2-weighted, diffusion magnetic resonance imaging [MRI], resting-state functional MRI, spectroscopy, arterial spin labeling) at baseline and at 2 years. Group differences in rates of change were assessed using linear mixed effects models. Results. One hundred twenty-three PLWH and 78 HIV-negative controls completed longitudinal assessments (median interval, 1.97 years). There were no differences between PLWH and HIV-negative controls in age, sex, years of education, smoking or alcohol use. At baseline, PLWH had poorer global cognitive performance (P < .01), lower gray matter volume (P = .04), higher white matter hyperintensity load (P = .02), abnormal white matter microstructure (P < .005), and greater brain-predicted age difference (P = .01). Longitudinally, there were no significant differences in rates of change in any neuroimaging measure between PLWH and HIV-negative controls (P > .1). Cognitive performance was longitudinally stable in both groups. Conclusions. We found no evidence that middle-aged PLWH, when receiving successful treatment, are at increased risk of accelerated aging-related brain changes or cognitive decline over 2 years. [ABSTRACT FROM AUTHOR]

Background: Brain structural abnormalities have been reported in persons living with human immunodeficiency virus (HIV; PLWH) who are receiving suppressive combination antiretroviral therapy (cART), but their pathophysiology remains unclear.Methods: We investigated factors associated with brain tissue volumes and white matter microstructure (fractional anisotropy) in 134 PLWH receiving suppressive cART and 79 comparable HIV-negative controls, aged ≥45 years, from the Comorbidity in Relation to AIDS cohort, using multimodal neuroimaging and cerebrospinal fluid biomarkers.Results: Compared with controls, PLWH had lower gray matter volumes (-13.7 mL; 95% confidence interval, -25.1 to -2.2) and fractional anisotropy (-0.0073; 95% confidence interval, -.012 to -.0024), with the largest differences observed in those with prior clinical AIDS. Hypertension and the soluble CD14 concentration in cerebrospinal fluid were associated with lower fractional anisotropy. These associations were independent of HIV serostatus (Pinteraction = .32 and Pinteraction = .59, respectively) and did not explain the greater abnormalities in brain structure in relation to HIV infection.Conclusions: The presence of lower gray matter volumes and more white matter microstructural abnormalities in well-treated PLWH partly reflect a combination of historical effects of AIDS, as well as the more general influence of systemic factors, such as hypertension and ongoing neuroinflammation. Additional mechanisms explaining the accentuation of brain structure abnormalities in treated HIV infection remain to be identified. [ABSTRACT FROM AUTHOR]

This study aims to evaluate the relation between a cluster of neuropsychiatric symptoms related to cholinergic deficiency and degradation of the cortical cholinergic projections which project from the nucleus basalis of Meynert to the cerebral cortex. An atlas of the pathway from the nucleus basalis to the cortex (NbM cortical pathway) was constructed using diffusion tensor imaging and tractography in 87 memory clinic patients. Structural degradation was considered to be represented by lower fractional anisotropy (FA) and higher mean diffusivity (MD). Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory. A predefined cluster including agitation, anxiety, apathy, delusions, hallucinations, and irritability was labeled as the cholinergic deficiency syndrome (CDS). In regression analyses, lower FA and higher MD in the NbM cortical pathway were associated with CDS symptoms but not with other neuropsychiatric symptoms. These associations were independent of cerebral atrophy and overall FA or MD. There was no association between interruption of the NbM cortical pathway by white matter hyperintensities and CDS symptoms. Cox regression suggested a trend for higher mortality with lower FA in the NbM cortical pathway may exist. These findings provide anatomical support for the hypothesis that degradation of the cholinergic projections from the nucleus basalis of Meynert may lead to a distinct clinical syndrome. Future studies could use our results to test the utility of assessing NbM projection integrity to identify patients who may benefit from cholinergic treatment or with a worse prognosis. [ABSTRACT FROM AUTHOR]

Pathological gambling (PG) is a behavioral addiction characterized by an inability to stop gambling despite the negative consequences, which may be mediated by cognitive flexibility deficits. Indeed, impaired cognitive flexibility has previously been linked to PG and also to reduced integrity of white matter connections between the basal ganglia and the prefrontal cortex. It remains unclear, however, how white matter integrity problems relate to cognitive inflexibility seen in PG. We used a cognitive switch paradigm during functional magnetic resonance imaging in pathological gamblers (PGs; n = 26) and healthy controls (HCs; n = 26). Cognitive flexibility performance was measured behaviorally by accuracy and reaction time on the switch task, while brain activity was measured in terms of blood oxygen level-dependent responses. We also used diffusion tensor imaging on a subset of data (PGs = 21; HCs = 21) in combination with tract-based spatial statistics and probabilistic fiber tracking to assess white matter integrity between the basal ganglia and the dorsolateral prefrontal cortex. Although there were no significant group differences in either task performance, related neural activity or tract-based spatial statistics, PGs did show decreased white matter integrity between the left basal ganglia and prefrontal cortex. Our results complement and expand similar findings from a previous study in alcohol-dependent patients. Although we found no association between white matter integrity and task performance here, decreased white matter connections may contribute to a diminished ability to recruit prefrontal networks needed for regulating behavior in PG. Hence, our findings could resonate an underlying risk factor for PG, and we speculate that these findings may extend to addiction in general. [ABSTRACT FROM AUTHOR]

Introduction High-grade chondrosarcoma, high-grade glioma and intrahepatic cholangiocarcinoma are aggressive types of cancer with a dismal outcome. This is due to the lack of effective treatment options, emphasising the need for novel therapies. Mutations in the genes IDH1 and IDH2 (isocitrate dehydrogenase 1 and 2) occur in 60% of chondrosarcoma, 80% of WHO grade II–IV glioma and 20% of intrahepatic cholangiocarcinoma. IDH1/2-mutated cancer cells produce the oncometabolite D-2-hydroxyglutarate (D-2HG) and are metabolically vulnerable to treatment with the oral antidiabetic metformin and the oral antimalarial drug chloroquine. Methods and analysis We describe a dose-finding phase Ib/II clinical trial, in which patients with IDH1/2-mutated chondrosarcoma, glioma and intrahepatic cholangiocarcinoma are treated with a combination of metformin and chloroquine. Dose escalation is performed according to a 3+3 dose-escalation scheme. The primary objective is to determine the maximum tolerated dose to establish the recommended dose for a phase II clinical trial. Secondary objectives of the study include (1) determination of pharmacokinetics and toxic effects of the study therapy, for which metformin and chloroquine serum levels will be determined over time; (2) investigation of tumour responses to metformin plus chloroquine in IDH1/2-mutated cancers using CT/MRI scans; and (3) whether tumour responses can be measured by non-invasive D-2HG measurements (mass spectrometry and magnetic resonance spectroscopy) of tumour tissue, serum, urine, and/or bile or next-generation sequencing of circulating tumour DNA (liquid biopsies). This study may open a novel treatment avenue for IDH1/2-mutated high-grade chondrosarcoma, glioma and intrahepatic cholangiocarcinoma by repurposing the combination of two inexpensive drugs that are already approved for other indications. Ethics and dissemination This study has been approved by the medical-ethical review committee of the Academic Medical Center, Amsterdam, The Netherlands. The report will be submitted to a peer-reviewed journal. [ABSTRACT FROM AUTHOR]