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Objective: Offspring whose parents have Alzheimer disease (AD) are at increased risk for developing dementia. Patients with AD typically exhibit disruptions in the default mode network (DMN). The aim of this study was to investigate the effect of a family history of late onset AD on DMN integrity in cognitively normal individuals. In particular, we determined whether a family history effect is detectable in apolipoprotein E (APOE) ε4 allele noncarriers., Methods: We studied a cohort of 348 cognitively normal participants with or without family history of late onset AD. DMN integrity was assessed by resting state functional connectivity magnetic resonance imaging., Results: A family history of late onset AD was associated with reduced resting state functional connectivity between particular nodes of the DMN, namely the posterior cingulate and medial temporal cortex. The observed functional connectivity reduction was not attributable to medial temporal structural atrophy. Importantly, we detected a family history effect on DMN functional connectivity in APOE ε4 allele noncarriers., Interpretation: Unknown genetic factors, embodied in a family history of late onset AD, may affect DMN integrity prior to cognitive impairment., (Copyright © 2012 American Neurological Association.)

Alzheimer's disease (AD) is the most common cause of dementia. Much is known concerning AD pathophysiology but our understanding of the disease at the systems level remains incomplete. Previous AD research has used resting-state functional connectivity magnetic resonance imaging (rs-fcMRI) to assess the integrity of functional networks within the brain. Most studies have focused on the default-mode network (DMN), a primary locus of AD pathology. However, other brain regions are inevitably affected with disease progression. We studied rs-fcMRI in five functionally defined brain networks within a large cohort of human participants of either gender (n = 510) that ranged in AD severity from unaffected [clinical dementia rating (CDR) 0] to very mild (CDR 0.5) to mild (CDR 1). We observed loss of correlations within not only the DMN but other networks at CDR 0.5. Within the salience network (SAL), increases were seen between CDR 0 and CDR 0.5. However, at CDR 1, all networks, including SAL, exhibited reduced correlations. Specific networks were preferentially affected at certain CDR stages. In addition, cross-network relations were consistently lost with increasing AD severity. Our results demonstrate that AD is associated with widespread loss of both intranetwork and internetwork correlations. These results provide insight into AD pathophysiology and reinforce an integrative view of the brain's functional organization.

Throughout middle-childhood, inhibitory processes, which underlie many higher order cognitive tasks, are developing. Little is known about how inhibitory processes change as a task becomes conceptually more difficult during these important years. In adults, as Go/NoGo tasks become more difficult there is a systematic decrease in the P3NoGo response, indicating the use of effective inhibitory strategies (Maguire et al., 2009). This paper investigates the age at which children employ similar inhibitory strategies by studying behavioral and Event Related Potential (ERP) measures of response inhibition for three Go/NoGo tasks. Seventeen 7-8 year-olds and twenty 10-11-year-olds completed three Go/NoGo tasks that differed in the level of categorization necessary to respond. Both age groups displayed slower reaction times as the tasks became more difficult. Further, both groups displayed the predicted Go vs. NoGo P3 amplitude differences in the two simplest tasks, but no significant P3 differences for the most complex task. The reason for this pattern of responses was different in the different age groups. Similar to adults in previous work, the oldest children showed an attenuation of the P3 NoGo response with task difficulty, and no corresponding changes in the Go amplitude. The younger children displayed the opposite pattern, a significant increase in the Go amplitude with task difficulty, and no changes in the NoGo response. These response patterns indicate that efficient inhibitory strategies are developing throughout middle-childhood., (Copyright © 2011 Elsevier Inc. All rights reserved.)

A better understanding of carbon dioxide (CO(2)) effect on brain activity may have a profound impact on clinical studies using CO(2) manipulation to assess cerebrovascular reserve and on the use of hypercapnia as a means to calibrate functional magnetic resonance imaging (fMRI) signal. This study investigates how an increase in blood CO(2), via inhalation of 5% CO(2), may alter brain activity in humans. Dynamic measurement of brain metabolism revealed that mild hypercapnia resulted in a suppression of cerebral metabolic rate of oxygen (CMRO(2)) by 13.4% ± 2.3% (N=14) and, furthermore, the CMRO(2) change was proportional to the subject's end-tidal CO(2) (Et-CO(2)) change. When using functional connectivity MRI (fcMRI) to assess the changes in resting-state neural activity, it was found that hypercapnia resulted in a reduction in all fcMRI indices assessed including cluster volume, cross-correlation coefficient, and amplitude of the fcMRI signal in the default-mode network (DMN). The extent of the reduction was more pronounced than similar indices obtained in visual-evoked fMRI, suggesting a selective suppression effect on resting-state neural activity. Scalp electroencephalogram (EEG) studies comparing hypercapnia with normocapnia conditions showed a relative increase in low frequency power in the EEG spectra, suggesting that the brain is entering a low arousal state on CO(2) inhalation.

To study the interactions between semantic processing and motor response inhibition, we recorded scalp EEG as subjects performed a series of Go/NoGo response inhibition tasks whose response criteria depended on different levels of semantic processing. Three different tasks were used. The first required the subject to make a Go/NoGo decision based on pictures of one particular car or one particular dog. The second used pictures of different types of cars and of dogs, and the final task used stimuli that ranged across multiple types of objects and animals. We found that the theta-band EEG power recorded during the NoGo response was attenuated as a function of semantic complexity while the peak latency was delayed in only the most complex category task. Further, frontal alpha-band desynchronization was strongest for the simplest task and remained close to baseline for the other tasks. Finally, there was significant theta-band coherence between the frontal pole and pre-SMA for the NoGo conditions across tasks, which was not found in the Go trials. These findings provide information about how more rostral frontal regions interact with the pre-SMA during response inhibition across different stimuli and task demands: specifically, level of processing affects latency, difficulty affects amplitude, and coherence is affected by whether the decision is Go or NoGo., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Despite the importance of semantic relationships to our understanding of semantic knowledge, the nature of the neural processes underlying these abilities are not well understood. In order to investigate these processes, 20 healthy adults listened to thematically related (e.g., leash-dog), taxonomically related (e.g., horse-dog), or unrelated (e.g., desk-dog) noun pairs as their EEG was recorded. The data were analyzed using both event-related potentials (ERP) and event-related spectral perturbation (ERSP) analyses. The spatiotemporal ERP and ERSP results were analyzed further with principal component analysis (PCA). When comparing unrelated to related word pairs, the expected N400 effect was confirmed, as well as differences in theta and alpha oscillations. When comparing thematically and taxonomically related word pairs, the ERP revealed no significant differences, but the ERSP did. Specifically, theta power increased over right frontal areas for thematic versus taxonomic relationships and alpha power increased over parietal areas for taxonomic versus thematic relationships. The different oscillatory patterns over different brain regions suggest that thematic and taxonomic relationships engage distinct neural processes. Specifically, thematic relationships engage memory processes, while taxonomic relationships may require additional inhibitory or attention processes., (Copyright 2010 Elsevier Inc. All rights reserved.)

A new method is developed for analyzing the time-varying spectral content of EEG data collected in cognitive tasks. The goal is to extract and summarize the most salient features of numerical results, which span space, time, frequency, task conditions, and multiple subjects. Direct generalization of an established approach for analyzing event-related potentials, which uses sequential PCA followed by ANOVA to test for differences between conditions across subjects, gave unacceptable results. The new method, termed STAT-PCA, advocates statistical testing for differences between conditions within single subjects, followed by sequential PCA across subjects. In contrast to PCA-ANOVA, it is demonstrated that STAT-PCA gives results which: 1) isolate task-related spectral changes, 2) are insensitive to the precise definition of baseline power, 3) are stable under deletion of a random subject, and 4) are interpretable in terms of the group-averaged power. Furthermore, STAT-PCA permits the detection of activity that is not only different between conditions, but also common to both conditions, providing a complete yet parsimonious view of the data. It is concluded that STAT-PCA is well suited for analyzing the time-varying spectral content of EEG during cognitive tasks.

The involvement of the left temporal lobe in semantics and object naming has been repeatedly demonstrated in the context of language comprehension; however, its role in the mechanisms and time course for the retrieval of an integrated object memory from its constituent features have not been well delineated. In this study, 19 young adults were presented with two features of an object (e.g., "desert" and "humps") and asked to determine whether these two features were congruent to form a retrieval of a specific object ("camel") or incongruent and formed no retrieval while event-related potentials (ERP) were recorded. Beginning around 750 ms the ERP retrieval and nonretrieval waveforms over the left anterior fronto-temporal region show significance differences, indicating distinct processes for retrievals and nonretrievals. In addition to providing further data implicating the left frontal-anterior temporal region in object memory/retrieval, the results provide insight into the time course of semantic processing related to object memory retrieval in this region. The likely semantic process at 750 ms in this task would be coactivation of feature representations common to the same object. The consistency of this finding suggests that the process is stable across individuals. The potential clinical applications are discussed.