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Background Previous research has shown that the human brain can be represented as a complex functional network that is characterized by specific topological properties, such as clustering coefficient, characteristic path length, and global/local efficiency. Patients with psychotic disorder may have alterations in these properties with respect to controls, indicating altered efficiency of network organization. This study examined graph theoretical changes in relation to differential genetic risk for the disorder and aimed to identify clinical correlates. Methods Anatomical and resting-state MRI brain scans were obtained from 73 patients with psychotic disorder, 83 unaffected siblings, and 72 controls. Topological measures (i.e., clustering coefficient, characteristic path length, and small-worldness) were used as dependent variables in a multilevel random regression analysis to investigate group differences. In addition, associations with (subclinical) psychotic/cognitive symptoms were examined. Results Patients had a significantly lower clustering coefficient compared to siblings and controls, with no difference between the latter groups. No group differences were observed for characteristic path length and small-worldness. None of the topological properties were associated with (sub)clinical psychotic and cognitive symptoms. Conclusions The reduced ability for specialized processing (reflected by a lower clustering coefficient) within highly interconnected brain regions observed in the patient group may indicate state-related network alterations. There was no evidence for an intermediate phenotype and no evidence for psychopathology-related alterations. [ABSTRACT FROM AUTHOR]

FreeSurfer is a popular software package to measure cortical thickness and volume of neuroanatomical structures. However, little if any is known about measurement reliability across various data processing conditions. Using a set of 30 anatomical T1-weighted 3T MRI scans, we investigated the effects of data processing variables such as FreeSurfer version (v4.3.1, v4.5.0, and v5.0.0), workstation (Macintosh and Hewlett-Packard), and Macintosh operating system version (OSX 10.5 and OSX 10.6). Significant differences were revealed between FreeSurfer version v5.0.0 and the two earlier versions. These differences were on average 8.8±6.6% (range 1.3-64.0%) (volume) and 2.8±1.3% (1.1-7.7%) (cortical thickness). About a factor two smaller differences were detected between Macintosh and Hewlett-Packard workstations and between OSX 10.5 and OSX 10.6. The observed differences are similar in magnitude as effect sizes reported in accuracy evaluations and neurodegenerative studies. The main conclusion is that in the context of an ongoing study, users are discouraged to update to a new major release of either FreeSurfer or operating system or to switch to a different type of workstation without repeating the analysis; results thus give a quantitative support to successive recommendations stated by FreeSurfer developers over the years. Moreover, in view of the large and significant cross-version differences, it is concluded that formal assessment of the accuracy of FreeSurfer is desirable. [ABSTRACT FROM AUTHOR]

Background: The cerebral default mode network (DMN) can be mapped onto specific regions in the cerebellum, which are specifically vulnerable to atrophy in Alzheimer's disease (AD) patients.Objective: We set out to determine whether there are specific differences in the interaction between the cerebral and cerebellar DMN in amnestic mild cognitive impairment (aMCI) patients compared to healthy controls using resting-state functional MRI and whether these differences are relevant for memory performance.Methods: Eighteen patients with aMCI were age and education-matched to eighteen older adults and underwent 3T MR-imaging. We performed seed-based functional connectivity analysis between the cerebellar DMN seeds and the cerebral DMN.Results: Our results showed that compared to healthy older adults, aMCI patients showed lower anti-correlation between the cerebellar DMN and several cerebral DMN regions. Additionally, we showed that degradation of the anti-correlation between the cerebellar DMN and the medial frontal cortex is correlated with worse memory performance in aMCI patients.Conclusion: These findings provide evidence that the cerebellar DMN and cerebral DMN are negatively correlated during rest in older individuals, and suggest that the reduced anti-correlated impacts the modulatory role of the cerebellum on cognitive functioning, in particular on the executive component of memory functions in neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Pattern separation (PS) describes the process by which the brain discriminates similar stimuli from previously encoded stimuli. This fundamental process requires the intact processing by specific subfields in the hippocampus and can be examined using mnemonic discrimination tasks. Previous studies reported different patterns for younger and older individuals between mnemonic discrimination performance and hippocampal subfield activation. Here, we investigated the relationship between the lure discrimination index (LDI) and hippocampal subfield volume and activity across the adult lifespan (20–70 years old). Using ultra-high field functional and structural magnetic resonance imaging at 7 T, we found that lower DG volume and higher CA3 activation was associated with worse LDI performance in individuals (>60 years), suggesting that this higher activation may be an indication of aberrant neurodegenerative-related processes. In fact, higher activation in the CA1 and DG was associated with lower volumes in these subfields. For individuals around 40–50 years old, we observed that greater left and right DG volume, and greater activity in the CA3 was associated with lower LDI performance. Taken together, these results suggest that the relationship between memory and hippocampal subfield structure or function varies nonlinearly and possibly reciprocally with age, with midlife being a critically vulnerable period in life. [ABSTRACT FROM AUTHOR]

Cerebral small vessel disease (cSVD) and amyloid-β (Aβ) deposition often co-exist in (prodromal) dementia, and both types of pathology have been associated with neurodegeneration. We examined whether cSVD and Aβ have independent or interactive effects on hippocampal volume (HV) in a memory clinic population. We included 87 individuals with clinical diagnoses of Alzheimer's disease (AD) (n = 24), mild cognitive impairment (MCI) (n = 26), and subjective cognitive complaints (SCC) (n = 37). cSVD magnetic resonance imaging markers included white matter hyperintensity (WMH) volume, lacunar infarct presence, and microbleed presence. Aβ pathology was assessed as cerebrospinal fluid-derived Aβ1 - 42 levels and dichotomized into normal or abnormal, and HV was determined by manual volumetric measurements. A linear hierarchical regression approach was applied for the detection of additive or interaction effects between cSVD and Aβ on HV in the total participant group (n = 87) and in the non-demented group (including SCC and MCI individuals only, n = 63). The results revealed that abnormal Aβ and lacunar infarct presence were independently associated with lower HV in the non-demented individuals. Interestingly, Aβ and WMH pathology interacted in the non-demented individuals, such that WMH had a negative effect on HV in individuals with abnormal CSF Aβ42 levels, but not in individuals with normal CSF Aβ42 levels. These associations were not present when individuals with AD were included in the analyses. Our observations suggest that relatively early on in the disease process older individuals with abnormal Aβ levels are at an increased risk of accelerated disease progression when concomitant cSVD is present. [ABSTRACT FROM AUTHOR]

Background: Research suggests that altered interregional connectivity in specific networks, such as the default mode network (DMN), is associated with cognitive and psychotic symptoms in schizophrenia. In addition, frontal and limbic connectivity alterations have been associated with trauma, drug use and urban upbringing, though these environmental exposures have never been examined in relation to DMN functional connectivity in psychotic disorder. Methods: Resting-state functional MRI scans were obtained from 73 patients with psychotic disorder, 83 non-psychotic siblings of patients with psychotic disorder and 72 healthy controls. Posterior cingulate cortex (PCC) seed-based correlation analysis was used to estimate functional connectivity within the DMN. DMN functional connectivity was examined in relation to group (familial risk), group × environmental exposure (to cannabis, developmental trauma and urbanicity) and symptomatology. Results: There was a significant association between group and PCC connectivity with the inferior parietal lobule (IPL), the precuneus (PCu) and the medial prefrontal cortex (MPFC). Compared to controls, patients and siblings had increased PCC connectivity with the IPL, PCu and MPFC. In the IPL and PCu, the functional connectivity of siblings was intermediate to that of controls and patients. No significant associations were found between DMN connectivity and (subclinical) psychotic/cognitive symptoms. In addition, there were no significant interactions between group and environmental exposures in the model of PCC functional connectivity. Discussion: Increased functional connectivity in individuals with (increased risk for) psychotic disorder may reflect trait-related network alterations. The within-network “connectivity at rest” intermediate phenotype was not associated with (subclinical) psychotic or cognitive symptoms. The association between familial risk and DMN connectivity was not conditional on environmental exposure. [ABSTRACT FROM AUTHOR]

Objective: To prospectively assess the relation between carotid plaque characteristics and the development of new cerebral white matter lesions (WMLs) at MRI. Methods: Fifty TIA/stroke patients with ipsilateral 30-69% carotid stenosis underwent MRI of the plaque at baseline. Total plaque volume and markers of vulnerability to thromboembolism (lipid-rich necrotic core [LRNC] volume, fibrous cap [FC] status, and presence of intraplaque hemorrhage [IPH]) were assessed. All patients also underwent brain MRI at baseline and after one year. Ipsilateral cerebral WMLs were quantified with a semiautomatic method. Results: MeanWML volume significantly increased over a one-year period (6.52 vs. 6.97 mm3, P = 0.005).WML volume at baseline and WML progression did not significantly differ (P>0.05) between patients with 30-49% and patients with 50-69% stenosis. There was a significant correlation between total plaque volume and baseline ipsilateral WML volume (Spearman r = 0.393, P = 0.005). There was no significant correlation between total plaque volume and ipsilateral WML progression. There were no significant associations between LRNC volume andWML volume at baseline andWML progression.WML volume at baseline and WML progression did not significantly differ between patients with a thick and intact FC and patients with a thin and/or ruptured FC. WML volume at baseline and WML progression also did not significantly differ between patients with and without IPH. Conclusion: The results of this study indicate that carotid plaque burden is significantly associated with WML severity, but that there is no causal relationship between carotid plaque vulnerability and the occurrence of WMLs. [ABSTRACT FROM AUTHOR]

Microvascular dysfunction (MVD) is a common pathophysiological change that occurs in various diseases, such as type 2 diabetes mellitus (T2DM), heart failure, dementia, and depression. Recent technical advances have enabled noninvasive measurement and quantification of microvascular changes in humans. In this paper, we describe the protocols of the microvascular measurements applied in the Maastricht Study, an ongoing prospective, population-based cohort study of persons aged 40–75 years being carried out in the southern part of the Netherlands (baseline data assessment, November 2010–January 2020). The study includes a variety of noninvasive measurements in skin, retina, brain, and sublingual tissue, as well as plasma and urine biomarker assessments. Following this, we summarize our main findings involving these microvascular measurements through the end of 2018. Finally, we provide a brief perspective on future microvascular investigations within the framework of the Maastricht Study. [ABSTRACT FROM AUTHOR]

Previous research has shown that asymmetry of brain activity is decreased in older adults. This study investigates whether cortical gray matter asymmetry also shows age-related differences, and whether gray matter asymmetry differs between cognitively stable persons and persons who have shown profound age-related declines in cognitive functioning. In addition, we have examined whether prodromal dementia affects the study outcome. The gray matter volumes of seven prefrontal and temporal regions of interest were delineated on T1-weighted MRI scans in 70 adults aged between 52 and 84 years. Statistical analyses were conducted with and without participants who developed dementia within 6 years after the MRI scan session. It was found that asymmetry did not differ over the age range of 52-84 years of age. This result did not change when data from participants who were diagnosed with dementia within 6 years after MRI assessment were excluded from the analysis. In addition, no gray matter asymmetry differences were found between cognitively stable participants and participants who showed cognitive decline. We conclude that alterations in gray matter asymmetry may not be part of the healthy aging process. [ABSTRACT FROM AUTHOR]