We investigate the neural basis of two routes to visual distraction: salient stimuli capture attention in a bottom-up fashion and the reappearance of task-irrelevant items that are being actively maintained in working memory can lead to distraction via top-down, but automatic, guidance of attention. Bottom-up, stimulus-driven distraction has typically been associated with a ventral network incorporating the inferior frontal gyrus and temporoparietal junction. A dorsal network including the superior frontal gyrus, superior parietal cortex and intraparietal sulcus is known to underlie the voluntary, top-down control of attention. Here we show that the ventral attention network may be modulated in a top-down manner by task-irrelevant memory signals. Furthermore, we delineate how the biasing of attention by these bottom-up and top-down sources of visual distraction is modulated by changes in connectivity among critical nodes of ventral and dorsal frontoparietal regions. The findings further our understanding of the neural circuitry that mediates the control of human visual attention.
The single nucleotide polymorphism rs10503253 within the CUB and Sushi multiple domains-1 (CSMD1) gene on 8p23.2 has been identified as genome-wide significant for schizophrenia (SZ). This gene is of unknown function but has been implicated in multiple neurodevelopmental disorders that impact upon cognition, leading us to hypothesize that an effect on brain structure and function underlying cognitive processes may be part of the mechanism by which CMSD1 increases illness risk. To test this hypothesis, we investigated this CSMD1 variant in vivo in healthy participants in a magnetic resonance imaging (MRI) study comprised of both fMRI of spatial working memory (N?=?50) and a voxel-based morphometry investigation of grey and white matter (WM) volume (N?=?150). Analyses of these data indicated that the risk "A" allele was associated with comparatively reduced cortical activations in BA18, that is, middle occipital gyrus and cuneus; posterior brain regions that support maintenance processes during performance of a spatial working memory task. Conversely, there was an absence of significant structural differences in brain volume (i.e., grey or WM). In accordance with previous evidence, these data suggest that CSMD1 may mediate brain function related to cognitive processes (i.e., executive function); with the relatively deleterious effects of the identified "A" risk allele on brain activity possibly constituting part of the mechanism by which CSMD1 increases schizophrenia risk.
A common polymorphism within the nitric oxide sythanse-1 (NOS1) gene (rs6490121), initially identified as risk variant for schizophrenia, has been associated with variation in working memory and IQ. Here we investigated how this variation might be mediated at the level of brain structure and function. In healthy individuals (N=157), voxel based morphometry was used to compare grey matter (GM) volume between homozygous and heterozygous carriers of the G allele (i.e. the allele associated with impaired cognition and schizophrenia risk) and homozygous carriers of the non-risk A allele. Functional brain imaging data were also acquired from 48 participants during performance of a spatial working memory (SWM) task, and analysed to determine any effect of NOS1 risk status. An a priori region-of-interest analysis identified a significant reduction in ventromedial prefrontal GM volume in G allele carriers. Risk carriers also exhibited altered patterns of activation in the prefrontal cortex, caudate, and superior parietal lobe, which were characteristic of abnormal increases in activation in frontoparietal working memory networks and a failure to disengage regions of the default mode network. These functional changes suggest a NOS1-mediated processing inefficiency, which may contribute to cognitive dysfunction in schizophrenia. While the mechanisms by which NOS1 may influence brain structure and/or function have not yet been well delineated, these data provide further evidence for a role of NOS1 in risk for schizophrenia via an impact upon cognitive function.
Working memory (WM) representations can bias visual selection to matching stimuli in the field. WM biases can, however, be modulated by the level of cognitive load, with WM guidance reduced as memory load increases. Here, we used functional magnetic resonance imaging to distinguish between competing hypotheses for the reduction of WM guidance under load: 1) poor neural representations of memory contents under high load, 2) strategic control at high loads to direct attention away from search distracters matching the WM content, and 3) reduction of frontal top-down biasing of visual areas with increasing memory loads. We show that matching between WM contents and the visual display appeared to be well represented in visual areas under high memory loads, despite a lack of WM guidance at the behavioral level. There was little engagement of "cognitive control" areas in the prefrontal cortex during search at high loads. More importantly, WM guidance at low loads engaged a set of frontal regions in the superior and inferior ventral frontal cortex. Functional connectivity analyses revealed frontal regions working in concert with occipital areas at low memory loads, but this coupling was disrupted by increased memory load. We discuss the implications for understanding the mechanisms supporting the interplay between WM and attention.
Emotional states linked to arousal and mood are known to affect the efficiency of cognitive performance. However, the extent to which memory processes may be affected by arousal, mood or their interaction is poorly understood.
Asymmetries of spatial attention are observed in both clinical and non-clinical populations. While lesions of the right hemisphere frequently result in symptoms of left neglect (right bias), the opposite pattern is often observed in healthy subjects, a phenomenon known as pseudoneglect. Pharmacological and animal studies have suggested a critical role for the catecholamines, in particular dopamine and noradrenaline, in modulating the direction and magnitude of spatial attentional bias. In the present study we investigated the effect of two catecholaminergic genes, DBH and DAT1, on performance in the Landmark task, a perceptual measure of spatial bias. 204 healthy participants performed the Landmark task and were genotyped for the DBH C-1021T and DAT1 3UTR variants. Homozygosity for the DBH T allele, which is associated with relatively increased dopamine and decreased noradrenaline levels, resulted in a significant increase in rightwards spatial bias relative to the C allele. Similarly, homozygosity for the DAT1 9-repeat allele, which is associated with reduced dopamine transporter density, and consequently increased dopamine availability relative to the 10-repeat allele, was found to result in a greater degree of rightward bias. An additive effect of the two markers was also observed, such that the greatest degree of rightward spatial bias was observed in participants who possessed the high dopamine alleles of both genes and the lowest degree in those without these alleles. These results provide the first evidence of genetic modulation of spatial bias in healthy adults.
Sustained attention is modulated by the neurotransmitter noradrenaline. The balance of dopamine and noradrenaline in the cortex is controlled by the DBH gene. The principal variant in this gene is a C/T change at position -1021, and the T allele at this locus is hypothesised to result in a slower rate of dopamine to noradrenaline conversion than the C allele. Two hundred participants who were genotyped for the DBH C-1021T marker performed the Sustained Attention to Response Task (SART). DBH genotype was found to significantly predict performance; participants with more copies of the T allele made more errors of commission, indicative of lapses in sustained attention. A significant negative correlation was also observed for all participants between errors of commission and mean reaction time. The decrease in noradrenaline occasioned by the T allele may impair sustained attention by reducing participants ability to remain alert throughout the task and by increasing their susceptibility to distractors.
The contents of working memory (WM) can both aid and disrupt the goal-directed allocation of visual attention. WM benefits attention when its contents overlap with goal-relevant stimulus features, but WM leads attention astray when its contents match features of currently irrelevant stimuli. Recent behavioral data have documented that WM biases of attention may be subject to strategic cognitive control processes whereby subjects are able to either enhance or inhibit the influence of WM contents on attention. However, the neural mechanisms supporting cognitive control over WM biases on attention are presently unknown. Here, we characterize these mechanisms by combining human functional magnetic resonance imaging with a task that independently manipulates the relationship between WM cues and attention targets during visual search (with WM contents matching either search targets or distracters), as well as the predictability of this relationship (100 vs 50% predictability) to assess participants ability to strategically enhance or inhibit WM biases on attention when WM contents reliably matched targets or distracter stimuli, respectively. We show that cues signaling predictable (> unpredictable) WM-attention relations reliably enhanced search performance, and that this strategic modulation of the interplay between WM contents and visual attention was mediated by a neuroanatomical network involving the posterior parietal cortex, the posterior cingulate, and medial temporal lobe structures, with responses in the hippocampus proper correlating with behavioral measures of strategic control of WM biases. Thus, we delineate a novel parieto-medial temporal pathway implementing cognitive control over WM biases to optimize goal-directed selection.
A single nucleotide polymorphism rs12807809 located upstream of the neurogranin (NRGN) gene has been identified as a risk variant for schizophrenia in recent genome-wide association studies. To date, there has been little investigation of the endophenotypic consequences of this variant, and our own investigations have suggested that the effects of this gene are not apparent at the level of cognitive function in patients or controls. Because the impact of risk variants may be more apparent at the level of brain, the aim of this investigation was to delineate whether NRGN genotype predicted variability in brain structure and/or function. Healthy individuals participated in structural (N = 140) and/or functional (N = 36) magnetic resonance imaging (s/fMRI). Voxel-based morphometry was used to compare gray and white matter volumes between carriers of the non-risk C allele (i.e., CC/CT) and those who were homozygous for the risk T allele. Functional imaging data were acquired during the performance of a spatial working memory task, and were also analyzed with respect to the difference between C carriers and T homozygotes. There was no effect of the NRGN variant rs12807809 on behavioral performance or brain structure. However, there was a main effect of genotype on brain activity during performance of the working memory task, such that while C carriers exhibited a load-independent decrease in left superior frontal gyrus/BA10, TT individuals failed to show a similar decrease in activity. The failure to disengage this ventromedial prefrontal region, despite preserved performance, may be indicative of a reduction in processing efficiency in healthy TT carriers. Although it remains to be established whether this holds true in larger samples and in patient cohorts, if valid, this suggests a potential mechanism by which NRGN variability might contribute to schizophrenia risk.
It remains an intriguing question why the medial temporal lobe (MTL) can display either attenuation or enhancement of neural activity following repetition of previously studied items. To isolate the role of encoding experience itself, we assessed neural repetition effects in the absence of any ongoing task demand or intentional orientation to retrieve. Experiment 1 showed that the hippocampus and surrounding MTL regions displayed neural repetition suppression (RS) upon repetition of past items that were merely attended during an earlier study phase but this was not the case following re-occurrence of items that had been encoded into working memory (WM). In this latter case a trend toward neural repetition enhancement (RE) was observed, though this was highly variable across individuals. Interestingly, participants with a higher degree of neural RE in the MTL complex displayed higher memory sensitivity in a later, surprise recognition test. Experiment 2 showed that massive exposure at encoding effected a change in the neural architecture supporting incidental repetition effects, with regions of the posterior parietal and ventral-frontal cortex in addition to the hippocampus displaying neural RE, while no neural RS was observed. The nature of encoding experience therefore modulates the expression of neural repetition effects in the MTL and the neocortex in the absence of memory goals.
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