The neural factors that account for the visual processing-speed reduction in aging are incompletely understood. Based on previous reports of age-related decreases in the intrinsic functional connectivity (iFC) within the cingulo-opercular network and its relevance for processing speed, we hypothesized that these decreases are associated with age-related reductions in visual processing speed. We used a whole-report task and modeling based on Bundesen's 'theory of visual attention' to parameterize visual processing speed in 91 healthy participants from 20 to 77 years old. iFC was estimated using independent-component analysis of resting-state fMRI data. From the clusters within the cingulo-opercular network exhibiting age-related decreased iFC, we found a cluster in the left insula to be particularly associated with visual processing speed and to mediate the age effect on visual speed. This mediation was not observed for age-related decreased iFC in other networks or for other attentional parameters. Our results point to the iFC in the cingulo-opercular network, represented by the left insula, as being a relevant marker for visual processing-speed changes in aging.Next, we performed two lines of control analysis. First, we checked whether the association between the cingulo-opercular network and visual processing speed is a specific one, as hypothesized, rather than being part of a more global relationship between changes in iFC and visual attention functions in general. That is, given the well-documented age-related decreases in iFC in the default-mode and dorsal-attention networks (see, e.g., Andrews-Hanna et al., 2007;Damoiseaux et al., 2008;Ferreira and Busatto, 2013), age-related reductions in visual processing speed might conceivably be associated with a general age-related decrease of iFC, rather than with that of the cingulo-opercular network exclusively. To check for this, (a) we examined whether visual processing speed C also relates to the iFC in other networks; and (b) we assessed whether the iFC in the cingulo-opercular network relates to other visual attention functions previously reported to change with aging, such as the visual perceptual threshold and VSTM storage capacity (see, e.g., McAvinue et al., 2012).Second, we controlled for potentially relevant confounds in the association between iFC in the cingulo-opercular network and visual processing speed. In particular, given that iFC in the cinguloopercular network has previously been found to be related to anxiety (see, e.g., Seeley et al., 2007) and anxiety level might in turn affect processing speed, we controlled for anxiety using the state-trait anxiety inventory (STAI;Laux et al., 1981;Spielberger et al., 1970). Two other potential confounds

Objectives: Event-related potentials (ERPs) can reflect differences in brain electrophysiology underlying cognitive functions in brain disorders such as dementia and mild cognitive impairment. To identify individuals at risk for Alzheimer disease (AD) we used high-density ERPs to examine brain physiology in young presymptomatic individuals (average age 34.2 years) who carry the E280A mutation in the presenilin-1 (PSEN1) gene and will go on to develop AD around the age of 45.Methods: Twenty-one subjects from a Colombian population with familial AD participated: 10 presymptomatic subjects positive for the PSEN1 mutation (carriers) and 11 siblings without the mutation (controls). Subjects performed a visual recognition memory test while 128-channel ERPs were recorded.Results: Despite identical behavioral performance, PSEN1 mutation carriers showed less positivity in frontal regions and more positivity in occipital regions, compared to controls. These differences were more pronounced during the 200-300 msec period. Discriminant analysis at this time interval showed promising sensitivity (72.7%) and specificity (81.8%) of the ERP measures to predict the presence of AD pathology. Conclusions:Presymptomatic PSEN1 mutation carriers show changes in brain physiology that can be detected by high-density ERPs. The relative differences observed showing greater frontal positivity in controls and greater occipital positivity in carriers indicates that control subjects may use frontally mediated processes to distinguish between studied and unstudied visual items, whereas carriers appear to rely more upon perceptual details of the items to distinguish between them. These findings also demonstrate the potential usefulness of ERP brain correlates as preclinical markers of AD. Neurology Recognition memory impairments in Alzheimer disease (AD) have been linked to neocortical association areas including temporal and parietal lobes.1 Event-related potentials (ERPs) are less expensive, more widely available, and more comfortable than many other imaging modalities (e.g., MRI, PET, SPECT). ERPs, along with other EEG measures, have proven to be a useful marker in neurodegenerative conditions. 2-5 ERP components of recognition memory are sensitive to decline in old age 6 and amnestic mild cognitive impairment (aMCI). 7 Studies have proposed ERPs as a sensitive method for early detection of AD, separating EEG activity related to AD pathology from normal aging. [8][9][10][11][12] Preclinical markers and early detection are increasingly

Simultanagnosia, an impairment in simultaneous object perception, has been attributed to deficits in visual attention and, specifically, to processing speed. Increasing visual attention deficits manifest over the course of Alzheimer's disease (AD), where the first changes are present already in its symptomatic predementia phase: amnestic mild cognitive impairment (aMCI). In this study, we examined whether patients with aMCI due to AD show simultaneous object perception deficits and whether and how these deficits relate to visual attention. Sixteen AD patients with aMCI and 16 age-, gender-, and education-matched healthy controls were assessed with a simultaneous perception task, with shapes presented in an adjacent, embedded, or overlapping manner, under free viewing without temporal constraints. We used a parametric assessment of visual attention based on the Theory of Visual Attention. Results show that patients make significantly more errors than controls when identifying overlapping shapes, which correlate with reduced processing speed. Our findings suggest simultaneous object perception deficits in very early AD, and a visual processing speed reduction underlying these deficits.

Separable visual attention functions are assumed to rely on distinct but interacting neural mechanisms. Bundesen's “theory of visual attention” (TVA) allows the mathematical estimation of independent parameters that characterize individuals' visual attentional capacity (i.e., visual processing speed and visual short-term memory storage capacity) and selectivity functions (i.e., top-down control and spatial laterality). However, it is unclear whether these parameters distinctively map onto different brain networks obtained from intrinsic functional connectivity, which organizes slowly fluctuating ongoing brain activity. In our study, 31 demographically homogeneous healthy young participants performed whole- and partial-report tasks and underwent resting-state functional magnetic resonance imaging (rs-fMRI). Report accuracy was modeled using TVA to estimate, individually, the four TVA parameters. Networks encompassing cortical areas relevant for visual attention were derived from independent component analysis of rs-fMRI data: visual, executive control, right and left frontoparietal, and ventral and dorsal attention networks. Two TVA parameters were mapped on particular functional networks. First, participants with higher (vs. lower) visual processing speed showed lower functional connectivity within the ventral attention network. Second, participants with more (vs. less) efficient top-down control showed higher functional connectivity within the dorsal attention network and lower functional connectivity within the visual network. Additionally, higher performance was associated with higher functional connectivity between networks: specifically, between the ventral attention and right frontoparietal networks for visual processing speed, and between the visual and executive control networks for top-down control. The higher inter-network functional connectivity was related to lower intra-network connectivity. These results demonstrate that separable visual attention parameters that are assumed to constitute relatively stable traits correspond distinctly to the functional connectivity both within and between particular functional networks. This implies that individual differences in basic attention functions are represented by differences in the coherence of slowly fluctuating brain activity.

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Background and purpose: Fatigue and low sleep quality in multiple sclerosis (MS) are closely related symptoms. Here, the associations between the brain's functional connectivity (FC) and fatigue and low sleep quality were investigated to determine the degree of neural distinctiveness of these symptoms.Method: A hundred and four patients with relapsing-remitting MS (age 38.9 ± 10.2 years, 66 females) completed the Modified Fatigue Impact Scale and the Pittsburgh Sleep Quality Index and underwent resting-state functional magnetic resonance imaging. FC was analyzed using independent-component analysis in sensorimotor, default-mode, fronto-parietal and basal-ganglia networks. Multiple linear regression models allowed us to test the association between FC and fatigue and sleep quality whilst controlling for one another as well as for demographic, disease-related and imaging variables. Results: Higher fatigue correlated with lower sleep quality (r = 0.54, p < 0.0001). Higher fatigue was associated with lower FC of the precentral gyrus in the sensorimotor network, the precuneus in the posterior default-mode network and the superior frontal gyrus in the left fronto-parietal network, independently of sleep quality. Lower sleep quality was associated with lower FC of the left intraparietal sulcus in the left frontoparietal network, independently of fatigue. Specific associations were found between fatigue and the sensorimotor network's global FC and between low sleep quality and the left fronto-parietal network's global FC. Conclusion: Despite the high correlation between fatigue and low sleep quality in the clinical picture, our findings clearly indicate that, on the neural level, fatigue and low sleep quality in MS are associated with decreased FC in distinct functional brain networks.

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Disclosure StatementThe authors declare no competing financial interests. AbbreviationsA-MTL = medial temporal lobes including amygdala; BOLD = blood oxygenation leveldependent signal; fMRI = functional magnetic resonance imaging; FWE = family wise error; ICA = independent component analysis; iFC = intrinsic functional connectivity; mICA = masked ICA; MTL = medial temporal lobes; rs-fMRI = resting state fMRI. AbstractIn mammals, the hippocampus, entorhinal, perirhinal, and parahippocampal cortices (i.e., core regions of the human medial temporal lobes, MTL) are locally interlaced with the adjacent amygdala nuclei at the structural and functional levels. At the global brain level, the human MTL has been described as part of the default mode network whereas amygdala nuclei as parts of the salience network, with both networks forming collectively a large-scale brain system supporting allostatic-interoceptive functions. We hypothesized (i) that intrinsic functional connectivity of slow activity fluctuations would reveal human MTL subsystems locally extending to the amygdala; and (ii) that these extended local subsystems would be globally embedded in large-scale brain systems supporting allostatic-interoceptive functions.From the resting-state fMRI data of three independent samples of cognitively healthy adults (one main and two replication samples: Ns = 101, 61, and 29, respectively), we analyzed the functional connectivity of fluctuating ongoing BOLD-activity within and outside the amygdala-MTL in a data-driven way using masked independent component and dualregression analyses. We found that at the local level MTL subsystems extend to the amygdala and are functionally organized along the longitudinal amygdala-MTL axis. These subsystems were characterized by a consistent involvement of amygdala, hippocampus, and entorhinal cortex, but a variable participation of perirhinal and parahippocampal regions. At the global level, amygdala-MTL subsystems selectively connected to salience, thalamic-brainstem, and default mode networksthe major cortical and subcortical parts of the allostatic-interoceptive system. These results provide evidence for integrated amygdala-MTL subsystems in humans, which are embedded within a larger allostatic-interoceptive system.