Older adults and particularly those at risk for developing dementia typically show a decline in episodic memory performance, which has been associated with altered memory network activity detectable via functional magnetic resonance imaging (fMRI). To quantify the degree of these alterations, a score has been developed as a putative imaging biomarker for successful aging in memory for older adults (Functional Activity Deviations during Encoding, FADE; Düzel et al., Hippocampus, 2011; 21: 803–814). Here, we introduce and validate a more comprehensive version of the FADE score, termed FADE‐SAME (Similarity of Activations during Memory Encoding), which differs from the original FADE score by considering not only activations but also deactivations in fMRI contrasts of stimulus novelty and successful encoding, and by taking into account the variance of young adults' activations. We computed both scores for novelty and subsequent memory contrasts in a cohort of 217 healthy adults, including 106 young and 111 older participants, as well as a replication cohort of 117 young subjects. We further tested the stability and generalizability of both scores by controlling for different MR scanners and gender, as well as by using different data sets of young adults as reference samples. Both scores showed robust age‐group‐related differences for the subsequent memory contrast, and the FADE‐SAME score additionally exhibited age‐group‐related differences for the novelty contrast. Furthermore, both scores correlate with behavioral measures of cognitive aging, namely memory performance. Taken together, our results suggest that single‐value scores of memory‐related fMRI responses may constitute promising biomarkers for quantifying neurocognitive aging.

Attention and memory deficits have been reported in heavy marijuana users, but these effects may be reversible after prolonged abstinence. It remains unclear whether the reversibility of these cognitive deficits indicates that chronic marijuana use does not alter cortical networks, or that such changes occur but the brain adapts to the drug-induced changes. Blood oxygenation-level dependent (BOLD) functional MRI (fMRI) was performed in 24 chronic marijuana users (12 abstinent and 12 active) and 19 age-, sex- and education-matched control subjects during a set of visual-attention tasks with graded levels of difficulty. Neuropsychological tests were also administered on each subject. The two marijuana user groups showed no significant difference in usage pattern (frequency or duration of use, age of first use, cumulative joints used, averaged >2000 joints) or estimated cumulative lifetime exposure of Delta-9-tetrahydrocannabinol (THC) (mean 168 +/- 45 versus 244 +/- 135 g). Despite similar task and cognitive test performance compared with control subjects, active and abstinent marijuana users showed decreased activation in the right prefrontal, medial and dorsal parietal, and medial cerebellar regions, but greater activation in various frontal, parietal and occipital brain regions during the visual-attention tasks (all with P < or = 0.001, corrected, cluster level). However, the BOLD signals in the right frontal and medial cerebellar regions normalized with duration of abstinence in the abstinent users. Active marijuana users, with positive urine tests for THC, showed greater activation in the frontal and medial cerebellar regions than abstinent marijuana users and greater usage of the reserve network (regions with load effect), suggesting a neuroadaptive state. Both earlier age of first use and greater estimated cumulative dose of THC exposure were related to lower BOLD signals in the right prefrontal region and medial cerebellum. The altered BOLD activation pattern in the attention network and hypoactivation of the cerebellum suggest neuroadaptive processes or alteration of brain development in chronic marijuana users. These changes also may be related to marijuana-induced alteration in resting cerebral blood volume/flow or downregulation of cannabinoid (CB1) receptors. The greater activation in the active compared with abstinent marijuana users demonstrates a neuroadaptive state in the setting of active marijuana use, while the long-term chronic effect of marijuana on the altered brain network may be reversible with prolonged abstinence.

Subject motion in MRI is a relevant problem in the daily clinical routine as well as in scientific studies. Since the beginning of clinical use of MRI, many research groups have developed methods to suppress or correct motion artefacts. This review focuses on rigid body motion correction of head and brain MRI and its application in diagnosis and research. It explains the sources and types of motion and related artefacts, classifies and describes existing techniques for motion detection, compensation and correction and lists established and experimental approaches. Retrospective motion correction modifies the MR image data during the reconstruction, while prospective motion correction performs an adaptive update of the data acquisition. Differences, benefits and drawbacks of different motion correction methods are discussed.

Human immunodeficiency virus (HIV)-positive patients commonly have attention and concentration problems. However, it remains unclear how HIV infection affects the attention network. Therefore, blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI) was performed in 36 subjects (18 HIV and 18 seronegative [SN] controls) during a set of visual attention tasks with increasing levels of attentional load. Compared with SN controls, HIV subjects showed similar task performance (accuracies and reaction times) but decreased activation in the normal visual attention network (dorsal parietal, bilateral prefrontal, and cerebellar regions) and increased activation in adjacent or contralateral brain regions. Cognitive performance (assessed with NPZ-8), CD4, and viral load all correlated with activated BOLD signals in brain regions that activated more in HIV subjects. Furthermore, HIV subjects activated more than SN controls in brain regions that showed load-dependent increase in activation (right prefrontal and right parietal regions) but less in regions that showed a saturation effect with increasing load. These findings suggest that HIV-associated brain injury leads to reduced efficiency in the normal attention network, thus requiring reorganization and increased usage of neural reserves to maintain performance during attention-requiring tasks. Exceeding the brain reserve capacity may lead to attention deficits and cognitive impairment in HIV patients.

The effects of chronic marijuana (MJ) use on brain function remain controversial. Because MJ is often used by human immunodeficiency virus (HIV) patients, the aim of this study was to evaluate whether chronic MJ use and HIV infection are associated with interactive or additive effects on brain chemistry and cognitive function. We evaluated 96 subjects (30 seronegative nondrug users, 24 MJ users, 21 HIV without MJ use, 21 HIV + MJ) using proton magnetic resonance spectroscopy and a battery of neuropsychological tests. The two primarily abstinent MJ user groups showed no significant differences on calculated estimates of lifetime grams of delta9-tetrahydrocannabinol exposure, despite some differences in usage pattern. The two HIV groups also had similar HIV disease severity (CD4 cell count, plasma viral load, HIV dementia staging, Karnofsky score). On two-way analyses of covariance, HIV infection (independent of MJ) was associated with trends for reduced N-acetyl aspartate (NA) in the parietal white matter and increased choline compounds (CHO) in the basal ganglia. In contrast, MJ (independent of HIV) was associated with decreased basal ganglia NA (−5.5%, p = 0.05), CHO (−10.6%, p = 0.04), and glutamate (−9.5%, p = 0.05), with increased thalamic creatine (+6.1%, p = 0.05). HIV + MJ was associated with normalization of the reduced glutamate in frontal white matter (interaction p = 0.01). After correction for age, education, or mood differences, MJ users had no significant abnormalities on neuropsychological test performance, and HIV subjects only had slower reaction times. These findings suggest chronic MJ use may lead to decreased neuronal and glial metabolites, but may normalize the decreased glutamate in HIV patients.

Objective-To determine whether brain activation changes in clinically and neurocognitively normal human immunodeficiency virus (HIV)-infected and in HIV-seronegative control (SN) participants over a 1-year period.Methods-Functional magnetic resonance imaging (fMRI) was performed in 32 SN and 31 HIV patients (all with stable combination antiretroviral treatment) at baseline and after 1 year. Each participant performed a set of visual attention tasks with increasing attentional load (from tracking two, three, or four balls). All HIV and SN participants had normal neuropsychological function at both examinations.Results-Over 1 year, HIV patients showed no change in their neurocognitive status or in task performance during fMRI. However, HIV patients showed significant 1-year increases in fMRI signals in the prefrontal and posterior parietal cortices for the more difficult tasks, whereas SN control participants showed only decreases in brain activation in these regions. This resulted in significant interactions between HIV status and time of study in left insula, left parietal, left temporal, and several frontal regions (left and right middle frontal gyrus, and anterior cingulate). Interpretation-Because fMRI task performance remained unchanged in both groups, the HIV patients appeared to maintain performance by increasing usage of the attention network, whereas the control participants reduced usage of the attention network after 1 year. These findings suggest improved efficiency or a practice effect in the SN participants but declined efficiency of the neural substrate in HIV patients, possibly because of ongoing brain injury associated with the HIV infection, despite their apparent stable clinical course.Human immunodeficiency virus (HIV) can invade the brain and cause encephalitis, leukoencephalopathy, axonal damage, and variable neuronal loss.1 These neuropathological processes are accompanied by microglial and glial activation,1 which, in turn, may lead to the release of neurotoxic substances that may further contribute to neuronal apoptosis or neuronal dysfunction. These neuropathological alterations may ultimately lead to the clinical This study extends prior work by evaluating whether performance and brain activation change after 1 year during a set of visual attention tasks. Based on prior cross-sectional results, and our expectation that ongoing neuroinflammation and infection with HIV would lead to chronic and progressive brain injury, we hypothesized that neuroasymptomatic, cognitively stable HIV patients would show load-dependent increases in BOLD signals after 1 year to compensate for decreased neural efficiency while maintaining task performance. In contrast, HIV-seronegative (SN) participants with relatively unchanged neural substrate would show no significant signal changes in fMRI signals and task performances, or possibly signal decreases caused by increased efficiency from practice effects. Patients and Methods Research ParticipantsSixty-three individuals (30 male and 1 female HIV-infect...

We present an ultrahigh resolution in vivo human brain magnetic resonance imaging (MRI) dataset. It consists of T1-weighted whole brain anatomical data acquired at 7 Tesla with a nominal isotropic resolution of 250 μm of a single young healthy Caucasian subject and was recorded using prospective motion correction. The raw data amounts to approximately 1.2 TB and was acquired in eight hours total scan time. The resolution of this dataset is far beyond any previously published in vivo structural whole brain dataset. Its potential use is to build an in vivo MR brain atlas. Methods for image reconstruction and image restoration can be improved as the raw data is made available. Pre-processing and segmentation procedures can possibly be enhanced for high magnetic field strength and ultrahigh resolution data. Furthermore, potential resolution induced changes in quantitative data analysis can be assessed, e.g., cortical thickness or volumetric measures, as high quality images with an isotropic resolution of 1 and 0.5 mm of the same subject are included in the repository as well.

Objective-The purpose of this paper was to determine whether antiretroviral medications, especially the nucleoside analogue reverse transcriptase inhibitors, lead to altered brain activation due to their potential neurotoxic effects in patients with human immunodeficiency virus (HIV) infection.Methods-Forty-two right-handed men were enrolled in three groups: seronegative controls (SN, n=18), HIV subjects treated with antiretroviral medications (HIV+ ARV, n=12), or not treated with antiretroviral medications (HIV+NARV, n=12). Each subject performed a set of visual attention tasks with increasing difficulty or load (tracking two, three or four balls) during functional magnetic resonance imaging.Results-HIV subjects, both groups combined, showed greater load-dependent increases in brain activation in the right frontal regions compared to . HIV+ARV additionally showed greater load-dependent increases in activation compared to SN in bilateral superior frontal regions (p-corrected=0.032) and a lower percent accuracy on the performance of the most difficult task (tracking four balls). Region of interest analyses further demonstrated that SN showed load-dependent decreases (with repeated trials despite increasing difficulty), while HIV subjects showed load-dependent increases in activation with the more difficult tasks, especially those on ARVs.Interpretation-These findings suggest that chronic ARV treatments may lead to greater requirement of the attentional network reserve and hence less efficient usage of the network and less practice effects in these HIV patients. As the brain has a limited reserve capacity, exhausting the reserve capacity in HIV+ARV would lead to declined performance with more difficult tasks that require more attention. Prior functional magnetic resonance imaging (fMRI) studies demonstrated increased usage of reserve brain regions during working memory and attention tasks in HIV patients with mild dementia as well as in those who were neuroasymptomatic (Ernst et al. 2002). With effective antiretroviral treatments (ARVs), HIV-infected individuals are living longer, and the full clinical manifestation of HIV-dementia is less common (Dore et al. 2003;Ghafouri et al. 2006). However, the prevalence of a milder form of cognitive impairment appears to be rising among HIV-infected individuals, possibly due to the longer duration of illness and the additional effect of aging in these patients. Although treatment with ARVs typically leads to improved cognitive performance in HIV patients with dementia or cognitive deficits (Larussa et al. 2006;Sacktor et al. 2006;Sacktor et al. 2000), some studies suggest that some ARV treatments may not benefit the cognitive performance of those with lower nadir CD4 counts (Cysique et al. 2006). In addition, patients treated with nucleoside analogue reverse transcriptase inhibitors (NRTIs) develop a varying degree of myopathy or neuropathy after long-term therapy (Dalakas 2001); however, the effects of these drugs on brain function are not well understood. As NRT...