Eric Feczko

Prediction of Individual Brain Maturity Using fMRI

Connectivity Map of the Brain The growing appreciation that clinically abnormal behaviors in children and adolescents may be influenced or perhaps even initiated by developmental miscues has stoked an interest in mapping normal human brain maturation. Several groups have documented changes in gray and white matter using structural and functional magnetic resonance imaging (fMRI) in cross-sectional and longitudinal studies. Dosenbach et al. (p. 1358) developed an index of resting-state functional connectivity (that is, how tightly neuronal activities in distinct brain regions are correlated while the subject is at rest or even asleep) from analyses of three independent data sets (each based on fMRI scans of 150 to 200 individuals from ages 6 to 35 years old). Long-range connections increased with age and short-range connections decreased, indicating that networks become sparser and sharper with brain maturation. Multivariate pattern analysis of 5-minute brain scans provides a measure of brain maturity. Group functional connectivity magnetic resonance imaging (fcMRI) studies have documented reliable changes in human functional brain maturity over development. Here we show that support vector machine-based multivariate pattern analysis extracts sufficient information from fcMRI data to make accurate predictions about individuals’ brain maturity across development. The use of only 5 minutes of resting-state fcMRI data from 238 scans of typically developing volunteers (ages 7 to 30 years) allowed prediction of individual brain maturity as a functional connectivity maturation index. The resultant functional maturation curve accounted for 55% of the sample variance and followed a nonlinear asymptotic growth curve shape. The greatest relative contribution to predicting individual brain maturity was made by the weakening of short-range functional connections between the adult brain’s major functional networks.

Activation of the fusiform gyrus when individuals with autism spectrum disorder view faces

Prior imaging studies have failed to show activation of the fusiform gyrus in response to emotionally neutral faces in individuals with autism spectrum disorder (ASD) [Critchley et al., Brain 124 (2001) 2059; Schultz et al., Arch. Gen. Psychiatry 57 (2000) 331]. However, individuals with ASD do not typically exhibit the striking behavioral deficits that might be expected to result from fusiform gyrus damage, such as those seen in prosopagnosia, and their deficits appear to extend well beyond face identification to include a wide range of impairments in social perceptual processing. In this study, our goal was to further assess the question of whether individuals with ASD have abnormal fusiform gyrus activation to faces. We used high-field (3 T) functional magnetic resonance imaging to study face perception in 11 adult individuals with autism spectrum disorder (ASD) and 10 normal controls. We used face stimuli, object stimuli, and sensory control stimuli (Fourier scrambled versions of the face and object stimuli) containing a fixation point in the center to ensure that participants were looking at and attending to the images as they were presented. We found that individuals with ASD activated the fusiform face area and other brain areas normally involved in face processing when they viewed faces as compared to non-face stimuli. These data indicate that the face-processing deficits encountered in ASD are not due to a simple dysfunction of the fusiform area, but to more complex anomalies in the distributed network of brain areas involved in social perception and cognition.

Differential effects of aging and Alzheimer's disease on medial temporal lobe cortical thickness and surface area.

The volume of parcellated cortical regions is a composite measure related to both thickness and surface area. It is not clear whether volumetric decreases in medial temporal lobe (MTL) cortical regions in aging and Alzheimers disease (AD) are due to thinning, loss of surface area, or both, nor is it clear whether aging and AD differ in their effects on these properties. Participants included 28 Younger Normals, 47 Older Normals, and 29 patients with mild AD. T1-weighted MRI data were analyzed using a novel semi-automated protocol (presented in a companion article) to delineate the boundaries of entorhinal (ERC), perirhinal (PRC), and posterior parahippocampal (PPHC) cortical regions and calculate their mean thickness, surface area, and volume. Compared to Younger Normals, Older Normals demonstrated moderately reduced ERC and PPHC volumes, which were due primarily to reduced surface area. In contrast, the expected AD-related reduction in ERC volume was produced by a large reduction in thickness with minimal additional effect (beyond that of aging) on surface area. PRC and PPHC also showed large AD-related reductions in thickness. Of all these MTL morphometric measures, ERC and PRC thinning were the best predictors of poorer episodic memory performance in AD. Although the volumes of MTL cortical regions may decrease with both aging and AD, thickness is relatively preserved in normal aging, while even in its mild clinical stage, AD is associated with a large degree of thinning of MTL cortex. These differential morphometric effects of aging and AD may reflect distinct biologic processes and ultimately may provide insights into the anatomic substrates of change in memory-related functions of MTL cortex.

Neuroanatomical correlates of personality in the elderly.

Extraversion and neuroticism are two important and frequently studied dimensions of human personality. They describe individual differences in emotional responding that are quite stable across the adult lifespan. Neuroimaging research has begun to provide evidence that neuroticism and extraversion have specific neuroanatomical correlates within the cerebral cortex and amygdala of young adults. However, these brain areas undergo alterations in size with aging, which may influence the nature of these personality factor-brain structure associations in the elderly. One study in the elderly demonstrated associations between perisylvian cortex structure and measures of self transcendence [Kaasinen, V., Maguire, R.P., Kurki, T., Bruck, A., Rinne, J.O., 2005. Mapping brain structure and personality in late adulthood. NeuroImage 24, 315-322], but the neuroanatomical correlates of extraversion and neuroticism, or other measures of the Five Factor Model of personality have not been explored. The purpose of the present study was to investigate the structural correlates of neuroticism and extraversion in healthy elderly subjects (n=29) using neuroanatomic measures of the cerebral cortex and amygdala. We observed that the thickness of specific lateral prefrontal cortex (PFC) regions, but not amygdala volume, correlates with measures of extraversion and neuroticism. The results suggest differences in the regional neuroanatomic correlates of specific personality traits with aging. We speculate that this relates to the influences of age-related structural changes in the PFC.

A Functional Magnetic Resonance Imaging Study of Amygdala Responses to Human Faces in Aging and Mild Alzheimer’s Disease

BACKGROUND Neuropsychiatric symptoms are very common even in mild stages of Alzheimers disease (AD). The amygdala exhibits very early pathology in AD, but amygdala function in mild AD has received relatively little attention. The current study investigates functional alterations in the amygdala in aging and mild AD, and their relationships with neuropsychiatric symptoms. METHODS Functional magnetic resonance imaging (fMRI) was used to examine and compare amygdala responses in 12 young and elderly controls and in 12 mild AD patients during viewing of neutral and emotional human facial expressions. RESULTS Amygdala responses in the young and elderly did not significantly differ from each other. However, the AD group had significantly greater amygdala responses to both neutral and emotional faces relative to elderly controls. This group effect was maintained when amygdala volume, sex and age were included as covariates in the analysis. Furthermore, amygdala activity correlated with the severity of irritability and agitation symptoms in AD. CONCLUSIONS The amygdala in patients with mild AD is excessively responsive to human faces relative to elderly controls. These amygdala functional alterations may represent a physiologic marker for certain neuropsychiatric manifestations of AD.

Early visual cortex organization in autism: an fMRI study

Autism is a neurodevelopmental disorder characterized by preserved visual abilities as well as a special profile for visual cognition. We examined the visual cortex of high-ability individuals with autism in order to assess whether the presence of abnormalities at the primary sensory level in autism could be the basis of their unusual pattern of visual cognitive abilities. We found that the early sensory visual areas are normally organized in individuals with autism, with a normal ratio between central versus peripheral visual field representation. We conclude that the differences observed in the visual capacities of individuals with autism are likely to arise from higher-level cognitive areas and functions, and are the result of top-down processes.

An MRI-based method for measuring volume, thickness and surface area of entorhinal, perirhinal, and posterior parahippocampal cortex

Several quantitative MRI-based protocols have been developed for measuring the volume of entorhinal (ERC), perirhinal (PRC), and posterior parahippocampal (PPHC) cortex. However, since the volume of a cortical region is a composite measure, relating directly to both thickness and surface area, it would be ideal to be able to quantify all of these morphometric measures, particularly since disease-related processes, such as Alzheimers disease (AD), may preferentially affect thickness. This study describes a novel protocol for measuring the thickness, surface area, and volume of these three medial temporal lobe (MTL) subregions. Participants included 29 younger normal subjects (ages 18-30), 47 older normal subjects (ages 66-90), and 29 patients with mild AD (ages 56-90). Cortical surface models were reconstructed from the gray/white and gray/cerebrospinal fluid boundaries, and a hybrid visualization approach was implemented to trace the ERC, PRC, and PPHC using both orthogonal MRI slice- and cortical surface-based visualization of landmarks. Anatomic variants of the collateral sulcus (CS) were classified in all 105 participants, and the relationship between CS variants and corresponding morphometric measures was examined. One CS variant - deep, uninterrupted CS not connected with nearby sulci - was the most common configuration and was associated with thinner cortex within the ERC and PRC regions. This novel protocol enables the reliable measurement of both the thickness and surface area of ERC, PRC, and PPHC.

Mental state attribution and the temporoparietal junction: an fMRI study comparing belief, emotion, and perception.

By age 2, children attribute referential mental states such as perceptions and emotions to themselves and others, yet it is not until age 4 that they attribute representational mental states such as beliefs. This raises an interesting question: is attribution of beliefs different from attribution of perceptions and emotions in terms of its neural substrate? To address this question with a high degree of anatomic specificity, we partitioned the TPJ, a broad area often found to be recruited in theory of mind tasks, into 2 neuroanatomically specific regions of interest: Superior Temporal Sulcus (STS) and Inferior Parietal Lobule (IPL). To maximize behavioral specificity, we designed a tightly controlled verbal task comprised of sets of single sentences--sentences identical except for the type of mental state specified in the verb (belief, emotion, perception, syntax control). Results indicated that attribution of beliefs more strongly recruited both regions of interest than did emotions or perceptions. This is especially surprising with respect to STS, since it is widely reported in the literature to mediate the detection of referential states--among them emotions and perceptions--rather than the inference of beliefs. An explanation is offered that focuses on the differences between verbal stimuli and visual stimuli, and between a process of sentence comprehension and a process of visual detection.

Motion-related artifacts in structural brain images revealed with independent estimates of in-scanner head motion.

Motion‐contaminated T1‐weighted (T1w) magnetic resonance imaging (MRI) results in misestimates of brain structure. Because conventional T1w scans are not collected with direct measures of head motion, a practical alternative is needed to identify potential motion‐induced bias in measures of brain anatomy. Head movements during functional MRI (fMRI) scanning of 266 healthy adults (20–89 years) were analyzed to reveal stable features of in‐scanner head motion. The magnitude of head motion increased with age and exhibited within‐participant stability across different fMRI scans. fMRI head motion was then related to measurements of both quality control (QC) and brain anatomy derived from a T1w structural image from the same scan session. A procedure was adopted to “flag” individuals exhibiting excessive head movement during fMRI or poor T1w quality rating. The flagging procedure reliably reduced the influence of head motion on estimates of gray matter thickness across the cortical surface. Moreover, T1w images from flagged participants exhibited reduced estimates of gray matter thickness and volume in comparison to age‐ and gender‐matched samples, resulting in inflated effect sizes in the relationships between regional anatomical measures and age. Gray matter thickness differences were noted in numerous regions previously reported to undergo prominent atrophy with age. Recommendations are provided for mitigating this potential confound, and highlight how the procedure may lead to more accurate measurement and comparison of anatomical features. Hum Brain Mapp 38:472–492, 2017.

Analysis of Cortical Shape in Children with Simplex Autism

We used surface-based morphometry to test for differences in cortical shape between children with simplex autism (n = 34, mean age 11.4 years) and typical children (n = 32, mean age 11.3 years). This entailed testing for group differences in sulcal depth and in 3D coordinates after registering cortical midthickness surfaces to an atlas target using 2 independent registration methods. We identified bilateral differences in sulcal depth in restricted portions of the anterior-insula and frontal-operculum (aI/fO) and in the temporoparietal junction (TPJ). The aI/fO depth differences are associated with and likely to be caused by a shape difference in the inferior frontal gyrus in children with simplex autism. Comparisons of average midthickness surfaces of children with simplex autism and those of typical children suggest that the significant sulcal depth differences represent local peaks in a larger pattern of regional differences that are below statistical significance when using coordinate-based analysis methods. Cortical regions that are statistically significant before correction for multiple measures are peaks of more extended, albeit subtle regional differences that may guide hypothesis generation for studies using other imaging modalities.