Elaine J. Anderson

Widespread age-related differences in the human brain microstructure revealed by quantitative magnetic resonance imaging

A pressing need exists to disentangle age-related changes from pathologic neurodegeneration. This study aims to characterize the spatial pattern and age-related differences of biologically relevant measures in vivo over the course of normal aging. Quantitative multiparameter maps that provide neuroimaging biomarkers for myelination and iron levels, parameters sensitive to aging, were acquired from 138 healthy volunteers (age range: 19–75 years). Whole-brain voxel-wise analysis revealed a global pattern of age-related degeneration. Significant demyelination occurred principally in the white matter. The observed age-related differences in myelination were anatomically specific. In line with invasive histologic reports, higher age-related differences were seen in the genu of the corpus callosum than the splenium. Iron levels were significantly increased in the basal ganglia, red nucleus, and extensive cortical regions but decreased along the superior occipitofrontal fascicle and optic radiation. This whole-brain pattern of age-associated microstructural differences in the asymptomatic population provides insight into the neurobiology of aging. The results help build a quantitative baseline from which to examine and draw a dividing line between healthy aging and pathologic neurodegeneration.

Larger Extrastriate Population Receptive Fields in Autism Spectrum Disorders

Previous behavioral research suggests enhanced local visual processing in individuals with autism spectrum disorders (ASDs). Here we used functional MRI and population receptive field (pRF) analysis to test whether the response selectivity of human visual cortex is atypical in individuals with high-functioning ASDs compared with neurotypical, demographically matched controls. For each voxel, we fitted a pRF model to fMRI signals measured while participants viewed flickering bar stimuli traversing the visual field. In most extrastriate regions, perifoveal pRFs were larger in the ASD group than in controls. We observed no differences in V1 or V3A. Differences in the hemodynamic response function, eye movements, or increased measurement noise could not account for these results; individuals with ASDs showed stronger, more reliable responses to visual stimulation. Interestingly, pRF sizes also correlated with individual differences in autistic traits but there were no correlations with behavioral measures of visual processing. Our findings thus suggest that visual cortex in ASDs is not characterized by sharper spatial selectivity. Instead, we speculate that visual cortical function in ASDs may be characterized by extrastriate cortical hyperexcitability or differential attentional deployment.

The Neural Correlates of Crowding-Induced Changes in Appearance

Summary Object recognition in the peripheral visual field is limited by crowding: the disruptive influence of nearby clutter [1, 2]. Despite its severity, little is known about the cortical locus of crowding. Here, we examined the neural correlates of crowding by combining event-related fMRI adaptation with a change-detection paradigm [3]. Crowding can change the appearance of objects, such that items become perceptually matched to surrounding objects; we used this change in appearance as a signature of crowding and measured brain activity that correlated with the crowded percept. Observers adapted to a peripheral patch of noise surrounded by four Gabor flankers. When crowded, the noise appears oriented and perceptually indistinguishable from the flankers. Consequently, substitution of the noise for a Gabor identical to the flankers (“change-same”) is rarely detected, whereas substitution for an orthogonal Gabor (“change-different”) is rarely missed. We predicted that brain areas representing the crowded percept would show repetition suppression in change-same trials but release from adaptation in change-different trials. This predicted pattern was observed throughout cortical visual areas V1–V4, increasing in strength from early to late visual areas. These results depict crowding as a multistage process, involving even the earliest cortical visual areas, with perceptual consequences that are increasingly influenced by later visual areas.

Involvement of prefrontal cortex in visual search

Visual search for target items embedded within a set of distracting items has consistently been shown to engage regions of occipital and parietal cortex, but the contribution of different regions of prefrontal cortex remains unclear. Here, we used fMRI to compare brain activity in 12 healthy participants performing efficient and inefficient search tasks in which target discriminability and the number of distractor items were manipulated. Matched baseline conditions were incorporated to control for visual and motor components of the tasks, allowing cortical activity associated with each type of search to be isolated. Region of interest analysis was applied to critical regions of prefrontal cortex to determine whether their involvement was common to both efficient and inefficient search, or unique to inefficient search alone. We found regions of the inferior and middle frontal cortex were only active during inefficient search, whereas an area in the superior frontal cortex (in the region of FEF) was active for both efficient and inefficient search. Thus, regions of ventral as well as dorsal prefrontal cortex are recruited during inefficient search, and we propose that this activity is related to processes that guide, control and monitor the allocation of selective attention.

Visual surround suppression in schizophrenia.

Compared to unaffected observers patients with schizophrenia (SZ) show characteristic differences in visual perception, including a reduced susceptibility to the influence of context on judgments of contrast – a manifestation of weaker surround suppression (SS). To examine the generality of this phenomenon we measured the ability of 24 individuals with SZ to judge the luminance, contrast, orientation, and size of targets embedded in contextual surrounds that would typically influence the target’s appearance. Individuals with SZ demonstrated weaker SS compared to matched controls for stimuli defined by contrast or size, but not for those defined by luminance or orientation. As perceived luminance is thought to be regulated at the earliest stages of visual processing our findings are consistent with a suppression deficit that is predominantly cortical in origin. In addition, we propose that preserved orientation SS in SZ may reflect the sparing of broadly tuned mechanisms of suppression. We attempt to reconcile these data with findings from previous studies.

Cortical network for gaze control in humans revealed using multimodal MRI.

Functional magnetic resonance imaging (fMRI) techniques allow definition of cortical nodes that are presumed to be components of large-scale distributed brain networks involved in cognitive processes. However, very few investigations examine whether such functionally defined areas are in fact structurally connected. Here, we used combined fMRI and diffusion MRI–based tractography to define the cortical network involved in saccadic eye movement control in humans. The results of this multimodal imaging approach demonstrate white matter pathways connecting the frontal eye fields and supplementary eye fields, consistent with the known connectivity of these regions in macaque monkeys. Importantly, however, these connections appeared to be more prominent in the right hemisphere of humans. In addition, there was evidence of a dorsal frontoparietal pathway connecting the frontal eye field and the inferior parietal lobe, also right hemisphere dominant, consistent with specialization of the right hemisphere for directed attention in humans. These findings demonstrate the utility and potential of using multimodal imaging techniques to define large-scale distributed brain networks, including those that demonstrate known hemispheric asymmetries in humans.

White Matter Microstructure and Cognitive Function

In recent years, diffusion-weighted magnetic resonance imaging (DW-MRI) has been increasingly used to explore the relationship between white matter structure and cognitive function. This technique uses the passive diffusion of water molecules to infer properties of the surrounding tissue. DW-MRI has been extensively employed to investigate how individual differences in behavior are related to variability in white matter microstructure on a range of different cognitive tasks and also to examine the effect experiential learning might have on brain structural connectivity. Using diffusion tensor tractography, large white matter pathways have been traced in vivo and used to explore patterns of white matter projections between different brain regions. Recent findings suggest that diffusion-weighted imaging might even be used to measure functional differences in water diffusion during task performance. This review describes some research highlights in diffusion-weighted imaging and how this technique can be employed to further our understanding of cognitive function.

Perceptual load affects spatial tuning of neuronal populations in human early visual cortex

Summary Withdrawal of attention from a visual scene as a result of perceptual load modulates overall levels of activity in human visual cortex [1], but its effects on cortical spatial tuning properties are unknown. Here we show attentional load at fixation affects the spatial tuning of population receptive fields (pRFs) in early visual cortex (V1–3) using functional magnetic resonance imaging (fMRI). We found that, compared to low perceptual load, high perceptual load yielded a ‘blurrier’ representation of the visual field surrounding the attended location and a centrifugal ‘repulsion’ of pRFs. Additional data and control analyses confirmed that these effects were neither due to changes in overall activity levels nor to eye movements. These findings suggest neural ‘tunnel vision’ as a form of distractor suppression under high perceptual load.

Neural correlates of spatial orienting in the human superior colliculus.

A natural visual scene contains more information than the visual system has the capacity to simultaneously process, requiring specific items to be selected for detailed analysis at the expense of others. Such selection and inhibition are fundamental in guiding search behavior, but the neural basis of these mechanisms remains unclear. Abruptly appearing visual items can automatically capture attention, but once attention has been directed away from the salient event, return to that same location is slowed. In non-human primates, signals associated with attentional capture (AC) and subsequent inhibition of return (IOR) have been recorded from the superior colliculus (SC)--a structure known to play a pivotal role in reflexive spatial orienting. Here, we sought to establish whether similar signals could be recorded from the human SC, as well as early retinotopic cortical visual areas, where signals associated with AC and IOR have yet to be investigated with respect to oculomotor responses. Using an optimized oculomotor paradigm together with high-field, high-spatial resolution functional magnetic resonance imaging and high-speed eye tracking, we demonstrate that BOLD signal changes recorded from the human SC correlate strongly with our saccadic measures of AC and IOR. A qualitatively similar pattern of responses was found for V1, but only the inhibitory response associated with IOR persisted through V2 and V3. Although the SC plays a role in mediating these automatic attentional biasing signals, the source of these signals is likely to lie in higher cortical areas.

Overlapping functional anatomy for working memory and visual search

Recent behavioural findings using dual-task paradigms demonstrate the importance of both spatial and non-spatial working memory processes in inefficient visual search (Anderson et al. in Exp Psychol 55:301–312, 2008). Here, using functional magnetic resonance imaging (fMRI), we sought to determine whether brain areas recruited during visual search are also involved in working memory. Using visually matched spatial and non-spatial working memory tasks, we confirmed previous behavioural findings that show significant dual-task interference effects occur when inefficient visual search is performed concurrently with either working memory task. Furthermore, we find considerable overlap in the cortical network activated by inefficient search and both working memory tasks. Our findings suggest that the interference effects observed behaviourally may have arisen from competition for cortical processes subserved by these overlapping regions. Drawing on previous findings (Anderson et al. in Exp Brain Res 180:289–302, 2007), we propose that the most likely anatomical locus for these interference effects is the inferior and middle frontal cortex of the right hemisphere. These areas are associated with attentional selection from memory as well as manipulation of information in memory, and we propose that the visual search and working memory tasks used here compete for common processing resources underlying these mechanisms.