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ABSTRACT: The default-mode network (DMN) has become a well accepted concept in cognitive and clinical neuroscience over the last decade, and perusal of the recent literature attests to a stimulating research field of cognitive and diagnostic applications (for example, (Andrews-Hanna et al., 2010; Koch et al., 2010; Sheline et al., 2009a; Sheline et al., 2009b; Uddin et al., 2008; Uddin et al., 2009; Weng et al., 2009; Yan et al., 2009)). However, a formal definition of what exactly constitutes a functional brain network is difficult to come by. In recent contributions, some researchers argue that the DMN is best understood as multiple interacting subsystems (Buckner et al., 2008) and have explored modular components of the DMN that have different functional specialization and could to some extent be identified separately (Fox et al., 2005; Uddin et al., 2009). Such conception of modularity seems to imply an opposite construct of a 'unified whole', but it is difficult to locate proponents of the idea of a DMN who are supplying constraints that can be brought to bear on data in rigorous tests. Our aim in this paper is to present a principled way of deriving a single covariance pattern as the neural substrate of the DMN, test to what extent its behavior tracks the coupling strength between critical seed regions, and investigate to what extent our stricter concept of a network is consistent with the already established findings about the DMN in the literature. We show that our approach leads to a functional covariance pattern whose pattern scores are a good proxy for the integrity of the connections between a medioprefrontal, posterior cingulate and parietal seed regions. Our derived DMN network thus has potential for diagnostic applications that are simpler to perform than computation of pairwise correlational strengths or seed maps.
Brain research 06/2012; 1468:38-51. · 2.46 Impact Factor
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ABSTRACT: We performed a Delayed-Item-Recognition task to investigate the neural substrates of non-verbal visual working memory with event-related fMRI ('Shape task'). 25 young subjects (mean age: 24.0 years; STD=3.8 years) were instructed to study a list of either 1, 2 or 3 unnamable nonsense line drawings for 3s ('stimulus phase' or STIM). Subsequently, the screen went blank for 7s ('retention phase' or RET), and then displayed a probe stimulus for 3s in which subjects indicated with a differential button press whether the probe was contained in the studied shape-array or not ('probe phase' or PROBE). Ordinal Trend Canonical Variates Analysis (Habeck et al., 2005a) was performed to identify spatial covariance patterns that showed a monotonic increase in expression with memory load during all task phases. Reliable load-related patterns were identified in the stimulus and retention phase (p<0.01), while no significant pattern could be discerned during the probe phase. Spatial covariance patterns that were obtained from an earlier version of this task (Habeck et al., 2005b) using 1, 3, or 6 letters ('Letter task') were also prospectively applied to their corresponding task phases in the current non-verbal task version. Interestingly, subject expression of covariance patterns from both verbal and non-verbal retention phases correlated positively in the non-verbal task for all memory loads (p<0.0001). Both patterns also involved similar frontoparietal brain regions that were increasing in activity with memory load, and mediofrontal and temporal regions that were decreasing. Mean subject expression of both patterns across memory load during retention also correlated positively with recognition accuracy (d(L)) in the Shape task (p<0.005). These findings point to similarities in the neural substrates of verbal and non-verbal rehearsal processes. Encoding processes, on the other hand, are critically dependent on the to-be-remembered material, and seem to necessitate material-specific neural substrates.
Brain research 05/2012; 1467:27-41. · 2.46 Impact Factor
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Elise Caccappolo,
Roy N Alcalay,
Helen Mejia-Santana,
Ming-X Tang, Brian Rakitin,
Llency Rosado,
Elan D Louis,
Cynthia L Comella,
Amy Colcher,
Danna Jennings, [......],
Ronald F Pfeiffer,
Laura Marsh,
Brad Hiner,
Andrew D Siderowf,
Barbara M Ross,
Miguel Verbitsky,
Sergey Kisselev,
Ruth Ottman,
Lorraine N Clark,
Karen S Marder
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ABSTRACT: The cognitive profile of early onset Parkinson's disease (EOPD) has not been clearly defined. Mutations in the parkin gene are the most common genetic risk factor for EOPD and may offer information about the neuropsychological pattern of performance in both symptomatic and asymptomatic mutation carriers. EOPD probands and their first-degree relatives who did not have Parkinson's disease (PD) were genotyped for mutations in the parkin gene and administered a comprehensive neuropsychological battery. Performance was compared between EOPD probands with (N = 43) and without (N = 52) parkin mutations. The same neuropsychological battery was administered to 217 first-degree relatives to assess neuropsychological function in individuals who carry parkin mutations but do not have PD. No significant differences in neuropsychological test performance were found between parkin carrier and noncarrier probands. Performance also did not differ between EOPD noncarriers and carrier subgroups (i.e., heterozygotes, compound heterozygotes/homozygotes). Similarly, no differences were found among unaffected family members across genotypes. Mean neuropsychological test performance was within normal range in all probands and relatives. Carriers of parkin mutations, whether or not they have PD, do not perform differently on neuropsychological measures as compared to noncarriers. The cognitive functioning of parkin carriers over time warrants further study.
Journal of the International Neuropsychological Society 01/2011; 17(1):91-100. · 2.76 Impact Factor
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Roy N Alcalay,
Helen Mejia-Santana,
Ming X Tang, Brian Rakitin,
Llency Rosado,
Barbara Ross,
Miguel Verbitsky,
Sergey Kisselev,
Elan D Louis,
Cynthia L Comella, [......],
Kevin Novak,
Joseph H Friedman,
Ronald Pfeiffer,
Laura Marsh,
Bradley Hiner,
Andrew Siderowf,
Ruth Ottman,
Lorraine N Clark,
Karen S Marder,
Elise Caccappolo
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ABSTRACT: While little is known about risk factors for cognitive impairment in early onset Parkinson disease (EOPD), postmortem studies have shown an association between dementia with Lewy bodies (DLB) and glucocerebrosidase (GBA) mutation. We compared Mini-Mental State Examination (MMSE) performance and self-reported cognitive impairment in 699 EOPD participants genotyped for mutations in parkin (PRKN), leucine-rich repeat kinase-2 (LRRK2), and GBA. Logistic regression was used to assess the association between reported cognitive impairment and MMSE score, as well as between GBA group membership and self-reported impairment and MMSE. GBA carriers reported more impairment, but MMSE performance did not differ among genetic groups. Detailed neuropsychological testing is required to explore the association between cognitive impairment and GBA mutations.
Journal of Clinical and Experimental Neuropsychology 02/2010; 32(7):775-9. · 2.13 Impact Factor
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ABSTRACT: The effect of aging on interval timing was examined using a choice time production task, which required participants to choose a key response based on the location of the stimulus, but to delay responding until after a learned time interval. Experiment 1 varied attentional demands of the response choice portion of the task by varying difficulty of stimulus-response mapping. Choice difficulty affected temporal accuracy equally in both age groups, but older participants' response latencies were more variable under more difficult response choice conditions. Experiment 2 tested the contribution of long-term memory to differences in choice time production between age groups over 3 days of testing. Direction of errors in time production between the two age groups diverged over the 3 sessions, but variability did not differ. Results from each experiment separately show age-related changes to attention and memory in temporal processing using different measures and manipulations in the same task.
Aging Neuropsychology and Cognition 02/2009; 16(3):285-310. · 1.07 Impact Factor
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ABSTRACT: To test competing models of age-related changes in brain functioning (capacity limitation, neural efficiency, compensatory reorganization, and dedifferentiation), young (n=40; mean age=25.1 years) and elderly (n=18; mean age=74.4 years) subjects performed a delayed item recognition task for visually presented letters with three set sizes (1, 3, or 6 letters) while being scanned with BOLD fMRI. Spatial patterns of brain activity corresponding to either the slope or y-intercept of fMRI signal with respect to set size during memory set encoding, retention delay, or probe stimulus presentation trial phases were compared between elder and young populations. Age effects on fMRI slope during encoding and on fMRI y-intercept during retention delay were consistent with neural inefficiency; age effects on fMRI slope during retention delay were consistent with dedifferentiation. None of the other fMRI signal components showed any detectable age effects. These results suggest that, even within the same task, the nature of brain activation changes with aging can vary based on cognitive process engaged.
Neurobiology of aging 06/2007; 28(5):784-98. · 5.94 Impact Factor
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ABSTRACT: Subjects (n = 40) performed a delayed item recognition task for visually presented letters with three set sizes (1, 3 or 6 letters). Accuracy was close to ceiling at all set sizes, so we took set size as a proxy for WM load (i.e. the amount of information being maintained in WM). Functional magnetic resonance imaging (fMRI) signal associated with the delay period increased in a nearly linear fashion with WM load in the left inferior frontal gyrus/anterior insula (possibly Broca's area, BA 44/45), right anterior insula, bilateral caudate, bilateral precentral gyrus (BA 6), bilateral middle frontal gyrus (BA 9/46), bilateral inferior parietal lobule (with foci in both BA 39 and 40), left superior parietal lobule (BA 7), medial frontal gyrus (BA 6), anterior cingulate gyrus (BA 32) and bilateral superior frontal gyrus (BA 8). These results lend support to the idea that at least some of the cortical mechanisms of WM maintenance, potentially rehearsal, exhibit a scaling with WM load. In contrast, the delay-related fMRI signal in hippocampus followed an inverted U-shape, being greatest during the intermediate level of WM load, with relatively lower values at the lowest and highest levels of WM load. This pattern of delay-related fMRI activity, orthogonal to WM load, is seemingly not consonant with a role for hippocampus in WM maintenance of phonologically codable stimuli. This finding could possibly be related more to the general familiarity of the letter stimuli than their phonological codability per se.
Cerebral Cortex 04/2005; 15(3):303-16. · 6.54 Impact Factor
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ABSTRACT: The study aimed to identify task-related brain activation networks whose change in expression exhibits subject differences as a function of differential susceptibility to sleep deprivation. Brain activity during a non-verbal recognition memory task was investigated in an event-related functional MRI paradigm both prior to and after 48 h of sleep deprivation. Nineteen healthy subjects participated. Regional covariance analysis was applied to data. An activation network pattern was identified whose expression decreased from pre- to post-sleep deprivation in 15 out 19 subjects (P < 0.05). Differential decrease in expression correlated with worsening performance in recognition accuracy (P < 0.05). Sites of de-activation were found in the posterior cerebellum, right fusiform gyrus and precuneus, and left lingual and inferior temporal gyri; increased activation was found in the bilateral insula, claustrum and right putamen. A network whose expression decreased after sleep deprivation and correlated with memory performance was identified. We conclude that this activation network plays a role in cognitive function during sleep deprivation.
Cerebral Cortex 05/2004; 14(5):496-502. · 6.54 Impact Factor
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ABSTRACT: There is epidemiologic and imaging evidence for the presence of cognitive reserve, but the neurophysiologic substrate of CR has not been established. In order to test the hypothesis that CR is related to aspects of neural processing, we used fMRI to image 19 healthy young adults while they performed a nonverbal recognition test. There were two task conditions. A low demand condition required encoding and recognition of single items and a titrated demand condition required the subject to encode and then recognize a larger list of items, with the study list size for each subject adjusted prior to scanning such that recognition accuracy was 75%. We hypothesized that individual differences in cognitive reserve are related to changes in neural activity as subjects moved from the low to the titrated demand task. To test this, we examined the correlation between subjects' fMRI activation and NART scores. This analysis was implemented voxel-wise in a whole brain fMRI dataset. During both the study and test phases of the recognition memory task we noted areas where, across subjects, there were significant positive and negative correlations between change in activation from low to titrated demand and the NART score. These correlations support our hypothesis that neural processing differs across individuals as a function of CR. This differential processing may help explain individual differences in capacity, and may underlie reserve against age-related or other pathologic changes.
Journal of Clinical and Experimental Neuropsychology 09/2003; 25(5):691-701. · 2.13 Impact Factor
