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1.  Correlation and heritability in neuroimaging datasets: A spatial decomposition approach with application to an fMRI study of twins 
NeuroImage  2011;59(2):1132-1142.
Advances in modern neuroimaging in combination with behavioral genetics have allowed neuroscientists to investigate how genetic and environmental factors shape human brain structure and function. Estimating the heritability of brain structure and function via twin studies has become one of the major approaches in studying the genetics of the brain. In a classical twin study, heritability is estimated by computing genetic and phenotypic variation based on the similarity of monozygotic and dizygotic twins. However, heritability has traditionally been measured for univariate, scalar traits, and it is challenging to assess the heritability of a spatial process, such as a pattern of neural activity. In this work, we develop a statistical method to estimate phenotypic variance and covariance at each location in a spatial process, which in turn can be used to estimate the heritability of a spatial dataset. The method is based on a dimensionally-reduced model of spatial variation in paired images, in which adjusted least squares estimates can be used to estimate the key model parameters. The advantage of the proposed method compared to conventional methods such as a voxelwise or mean-ROI approaches is demonstrated in both a simulation study and a real data study assessing genetic influence on patterns of brain activity in the visual and motor cortices in response to a simple visuomotor task.
doi:10.1016/j.neuroimage.2011.06.066
PMCID: PMC3219840  PMID: 21763433
Heritability; Intraclass Correlation; Twin Study; Spatial Analysis; Genetics
2.  Neural Broadening or Neural Attenuation? Investigating Age-Related Dedifferentiation in the Face Network in a Large Lifespan Sample 
Previous studies have found that cortical responses to different stimuli become less distinctive as people get older. This age-related dedifferentiation may reflect the broadening of the tuning curves of category-selective neurons (broadening hypothesis) or it may be due to decreased activation of category-selective neurons (attenuation hypothesis). In this study, we evaluated these hypotheses in the context of the face-selective neural network. Over 300 participants, ranging in age from 20 to 89 years, viewed images of faces, houses, and control stimuli in a functional magnetic resonance imaging session. Regions within the core face network and extended face network were identified in individual subjects. Activation in many of these regions became significantly less face-selective with age, confirming previous reports of age-related dedifferentiation. Consistent with the broadening hypothesis, this dedifferentiation in the fusiform face area (FFA) was driven by increased activation to houses. In contrast, dedifferentiation in the extended face network was driven by decreased activation to faces, consistent with the attenuation hypothesis. These results suggest that age-related dedifferentiation reflects distinct processes in different brain areas. More specifically, dedifferentiation in FFA activity may be due to broadening of the tuning curves for face-selective neurons, while dedifferentiation in the extended face network reflects reduced face- or emotion-selective activity.
doi:10.1523/JNEUROSCI.4494-11.2012
PMCID: PMC3361757  PMID: 22323727
3.  Neural Dissociation of Number from Letter Recognition and Its Relationship to Parietal Numerical Processing 
The visual recognition of letters dissociates from the recognition of numbers at both the behavioral and neural level. In this article, using fMRI, we investigate whether the visual recognition of numbers dissociates from letters, thereby establishing a double dissociation. In Experiment 1, participants viewed strings of consonants and Arabic numerals. We found that letters activated the left midfusiform and inferior temporal gyri more than numbers, replicating previous studies, whereas numbers activated a right lateral occipital area more than letters at the group level. Because the distinction between letters and numbers is culturally defined and relatively arbitrary, this double dissociation provides some of the strongest evidence to date that a neural dissociation can emerge as a result of experience. We then investigated a potential source of the observed neural dissociation. Specifically, we tested the hypothesis that lateralization of visual number recognition depends on lateralization of higher-order numerical processing. In Experiment 2, the same participants performed addition, subtraction, and counting on arrays of nonsymbolic stimuli varying in numerosity, which produced neural activity in and around the intraparietal sulcus, a region associated with higher-order numerical processing. We found that individual differences in the lateralization of number activity in visual cortex could be explained by individual differences in the lateralization of numerical processing in parietal cortex, suggesting a functional relationship between the two regions. Together, these results demonstrate a neural double dissociation between letter and number recognition and suggest that higher-level numerical processing in parietal cortex may influence the neural organization of number processing in visual cortex.
doi:10.1162/jocn_a_00085
PMCID: PMC3357212  PMID: 21736455
4.  Age differences in neural distinctiveness revealed by multi-voxel pattern analysis 
NeuroImage  2010;56(2):736-743.
Current theories of cognitive aging argue that neural representations become less distinctive in old age, a phenomenon known as dedifferentiation. The present study used multi-voxel pattern analysis (MVPA) to measure age differences in the distinctiveness of distributed patterns of neural activation evoked by different categories of visual images. We found that neural activation patterns within the ventral visual cortex were less distinctive among older adults. Further, we report that age differences in neural distinctiveness extend beyond the ventral visual cortex: older adults also showed decreased distinctiveness in early visual cortex, inferior parietal cortex, and medial and lateral prefrontal cortex. Neural distinctiveness scores in early and late visual areas were highly correlated, suggesting shared mechanisms of age-related decline. Finally, we investigated whether older adults can compensate for altered processing in visual cortex by encoding stimulus information across larger numbers of voxels within the visual cortex or in regions outside visual cortex. We found no evidence that older adults can increase the distinctiveness of distributed activation patterns, either within or beyond the visual cortex. Our results have important implications for theories of cognitive aging and highlight the value of MVPA to the study of neural coding in the aging brain.
doi:10.1016/j.neuroimage.2010.04.267
PMCID: PMC2962693  PMID: 20451629
aging; fMRI; MVPA; dedifferentiation; compensation; ventral visual cortex
5.  Investigating Unique Environmental Contributions to the Neural Representation of Written Words: A Monozygotic Twin Study 
PLoS ONE  2012;7(2):e31512.
The visual word form area (VWFA) is a region of left inferior occipitotemporal cortex that is critically involved in visual word recognition. Previous studies have investigated whether and how experience shapes the functional characteristics of VWFA by comparing neural response magnitude in response to words and nonwords. Conflicting results have been obtained, however, perhaps because response magnitude can be influenced by other factors such as attention. In this study, we measured neural activity in monozygotic twins, using functional magnetic resonance imaging. This allowed us to quantify differences in unique environmental contributions to neural activation evoked by words, pseudowords, consonant strings, and false fonts in the VWFA and striate cortex. The results demonstrate significantly greater effects of unique environment in the word and pseudoword conditions compared to the consonant string and false font conditions both in VWFA and in left striate cortex. These findings provide direct evidence for environmental contributions to the neural architecture for reading, and suggest that learning phonology and/or orthographic patterns plays the biggest role in shaping that architecture.
doi:10.1371/journal.pone.0031512
PMCID: PMC3275550  PMID: 22347490
6.  Age-Related Neural Dedifferentiation in the Motor System 
PLoS ONE  2011;6(12):e29411.
Recent neuroimaging studies using multi-voxel pattern analysis (MVPA) show that distributed patterns of brain activation elicited by different visual stimuli are less distinctive in older adults than in young adults. However, less is known about the effects of aging on the neural representation of movement. The present study used MVPA to compare the distinctiveness of motor representations in young and older adults. We also investigated the contributions of brain structure to age differences in the distinctiveness of motor representations. We found that neural distinctiveness was reduced in older adults throughout the motor control network. Although aging was also associated with decreased gray matter volume in these regions, age differences in motor distinctiveness remained significant after controlling for gray matter volume. Our results suggest that age-related neural dedifferentiation is not restricted to sensory perception and is instead a more general feature of the aging brain.
doi:10.1371/journal.pone.0029411
PMCID: PMC3245287  PMID: 22216274
7.  Evaluating Functional Localizers: The Case of the FFA 
NeuroImage  2009;50(1):56-71.
Functional localizers are routinely used in neuroimaging studies to test hypotheses about the function of specific brain areas. The specific tasks and stimuli used to localize particular regions vary widely from study to study even when the same cortical region is targeted. Thus, it is important to ask whether task and stimulus changes lead to differences in localization or whether localization procedures are largely immune to differences in tasks and contrasting stimuli. We present two experiments and a literature review that explore whether face localizer tasks yield differential localization in the fusiform gyrus as a function of task and contrasting stimuli. We tested standard localization tasks---passive viewing, 1-back, and 2-back memory tests---and did not find differences in localization based on task. We did, however, find differences in the extent, strength and patterns/reliabilities of the activation in the fusiform gyrus based on comparison stimuli (faces vs. houses compared to faces vs. scrambled stimuli).
doi:10.1016/j.neuroimage.2009.12.024
PMCID: PMC2825676  PMID: 20025980
8.  Neural specificity predicts fluid processing ability in older adults 
We investigated whether individual differences in neural specificity—the distinctiveness of different neural representations—could explain individual differences in cognitive performance in older adults. Neural specificity was estimated based on how accurately multivariate pattern analysis identified neural activation patterns associated with specific experimental conditions. Neural specificity calculated from a same-different task on two categories of visual stimuli (faces and houses) significantly predicted performance on a range of fluid processing behavioral tasks (dot-comparison, digit-symbol, Trails-A, Trails-B, verbal-fluency) in older adults, whereas it did not correlate with a measure of crystallized knowledge (Shipley-vocabulary). In addition, the neural specificity measure accounted for thirty percent of the variance in a composite measure of fluid processing ability. These results are consistent with the hypothesis that loss of neural specificity, or dedifferentiation, contributes to reduced fluid processing ability in old age.
doi:10.1523/JNEUROSCI.0853-10.2010
PMCID: PMC2913723  PMID: 20610760

Results 1-8 (8)