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1.  Digital reconstruction and morphometric analysis of human brain arterial vasculature from magnetic resonance angiography 
NeuroImage  2013;82:170-181.
Characterization of the complex branching architecture of cerebral arteries across a representative sample of the human population is important for diagnosing, analyzing, and predicting pathological states. Brain arterial vasculature can be visualized by magnetic resonance angiography (MRA). However, most MRA studies are limited to qualitative assessments, partial morphometric analyses, individual (or small numbers of) subjects, proprietary datasets, or combinations of the above limitations. Neuroinformatics tools, developed for neuronal arbor analysis, were used to quantify vascular morphology from 3 T time-of-flight MRA high-resolution (620 μm isotropic) images collected in 61 healthy volunteers (36/25 F/M, average age = 31.2 ± 10.7, range = 19–64 years). We present in-depth morphometric analyses of the global and local anatomical features of these arbors. The overall structure and size of the vasculature did not significantly differ across genders, ages, or hemispheres. The total length of the three major arterial trees stemming from the circle of Willis (from smallest to largest: the posterior, anterior, and middle cerebral arteries; or PCAs, ACAs, and MCAs, respectively) followed an approximate 1:2:4 proportion. Arterial size co-varied across individuals: subjects with one artery longer than average tended to have all other arteries also longer than average. There was no net right–left difference across the population in any of the individual arteries, but ACAs were more lateralized than MCAs. MCAs, ACAs, and PCAs had similar branch-level properties such as bifurcation angles. Throughout the arterial vasculature, there were considerable differences between branch types: bifurcating branches were significantly shorter and straighter than terminating branches. Furthermore, the length and meandering of bifurcating branches increased with age and with path distance from the circle of Willis. All reconstructions are freely distributed through a public database to enable additional analyses and modeling (cng.gmu.edu/brava).
doi:10.1016/j.neuroimage.2013.05.089
PMCID: PMC3971907  PMID: 23727319
2.  Superficial White Matter: Effects of Age, Sex, and Hemisphere 
Brain Connectivity  2013;3(2):146-159.
Abstract
Structural and diffusion imaging studies demonstrate effects of age, sex, and asymmetry in many brain structures. However, few studies have addressed how individual differences might influence the structural integrity of the superficial white matter (SWM), comprised of short-range association (U-fibers), and intracortical axons. This study thus applied a sophisticated computational analysis approach to structural and diffusion imaging data obtained from healthy individuals selected from the International Consortium for Brain Mapping (ICBM) database across a wide adult age range (n=65, age: 18–74 years, all Caucasian). Fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) were sampled and compared at thousands of spatially matched SWM locations and within regions-of-interest to examine global and local variations in SWM integrity across age, sex, and hemisphere. Results showed age-related reductions in FA that were more pronounced in the frontal SWM than in the posterior and ventral brain regions, whereas increases in RD and AD were observed across large areas of the SWM. FA was significantly greater in left temporoparietal regions in men and in the posterior callosum in women. Prominent leftward FA and rightward AD and RD asymmetries were observed in the temporal, parietal, and frontal regions. Results extend previous findings restricted to the deep white matter pathways to demonstrate regional changes in the SWM microstructure relating to processes of demyelination and/or to the number, coherence, or integrity of axons with increasing age. SWM fiber organization/coherence appears greater in the left hemisphere regions spanning language and other networks, while more localized sex effects could possibly reflect sex-specific advantages in information strategies.
doi:10.1089/brain.2012.0111
PMCID: PMC3634148  PMID: 23461767
aging; diffusion tensor imaging (DTI); fractional anisotropy (FA); magnetic resonance imaging (MRI); structural connectivity; U-fibers
3.  Entering Adolescence: Resistance to Peer Influence, Risky Behavior, and Neural Changes in Emotion Reactivity 
Neuron  2011;69(5):10.1016/j.neuron.2011.02.019.
SUMMARY
Adolescence is often described as a period of heightened reactivity to emotions paired with reduced regulatory capacities, a combination suggested to contribute to risk-taking and susceptibility to peer influence during puberty. However, no longitudinal research has definitively linked these behavioral changes to underlying neural development. Here, 38 neurotypical participants underwent two fMRI sessions across the transition from late childhood (10 years) to early adolescence (13 years). Responses to affective facial displays exhibited a combination of general and emotion-specific changes in ventral striatum (VS), ventromedial PFC, amygdala, and temporal pole. Furthermore, VS activity increases correlated with decreases in susceptibility to peer influence and risky behavior. VS and amygdala responses were also significantly more negatively coupled in early adolescence than in late childhood while processing sad and happy versus neutral faces. Together, these results suggest that VS responses to viewing emotions may play a regulatory role that is critical to adolescent interpersonal functioning.
doi:10.1016/j.neuron.2011.02.019
PMCID: PMC3840168  PMID: 21382560
4.  Mirroring others’ emotions relates to empathy and interpersonal competence in children 
NeuroImage  2007;39(4):10.1016/j.neuroimage.2007.10.032.
The mirror neuron system (MNS) has been proposed to play an important role in social cognition by providing a neural mechanism by which others’ actions, intentions, and emotions can be understood. Here functional magnetic resonance imaging was used to directly examine the relationship between MNS activity and two distinct indicators of social functioning in typically-developing children (aged 10.1 years±7 months): empathy and interpersonal competence. Reliable activity in pars opercularis, the frontal component of the MNS, was elicited by observation and imitation of emotional expressions. Importantly, activity in this region (as well as in the anterior insula and amygdala) was significantly and positively correlated with established behavioral measures indexing children’s empathic behavior (during both imitation and observation) and interpersonal skills (during imitation only). These findings suggest that simulation mechanisms and the MNS may indeed be relevant to social functioning in everyday life during typical human development.
doi:10.1016/j.neuroimage.2007.10.032
PMCID: PMC3840169  PMID: 18082427
5.  Longitudinal change in the neural bases of adolescent social self-evaluations: Effects of age and pubertal development 
Self-evaluations undergo significant transformation during early adolescence, developing in parallel with the heightened complexity of teenagers’ social worlds. Intuitive theories of adolescent development, based in part on animal work, suggest that puberty is associated with neural-level changes that facilitate a “social reorientation” (Nelson, Leibenluft, McClure, and Pine, 2005). However, direct tests of this hypothesis using neuroimaging are limited in humans. This longitudinal fMRI study examined neurodevelopmental trajectories associated with puberty, self-evaluations, and the presumed social reorientation during the transition from childhood to adolescence. Participants (N = 27, M age = 10.1 and 13.1 years at timepoints one and two, respectively) engaged in trait evaluations of two targets (the self and a familiar fictional other), across two domains of competence (social and academic). Responses in ventromedial PFC increased with both age and pubertal development during self-evaluations in the social domain, but not in the academic domain. These results suggest changes in social self-evaluations are intimately connected with biology, not just peer contexts, and provide important empirical support for the relationship between neurodevelopment, puberty, and social functioning.
doi:10.1523/JNEUROSCI.4074-12.2013
PMCID: PMC3809090  PMID: 23616547
6.  Age and experience shape developmental changes in the neural basis of language-related learning 
Developmental science  2011;14(6):1261-1282.
Very little is known about the neural underpinnings of language learning across the lifespan and how these might be modified by maturational and experiential factors. Building on behavioral research highlighting the importance of early word segmentation (i.e. the detection of word boundaries in continuous speech) for subsequent language learning, here we characterize developmental changes in brain activity as this process occurs online, using data collected in a mixed cross-sectional and longitudinal design. One hundred and fifty-six participants, ranging from age 5 to adulthood, underwent functional magnetic resonance imaging (fMRI) while listening to three novel streams of continuous speech, which contained either strong statistical regularities, strong statistical regularities and speech cues, or weak statistical regularities providing minimal cues to word boundaries. All age groups displayed significant signal increases over time in temporal cortices for the streams with high statistical regularities; however, we observed a significant right-to-left shift in the laterality of these learning-related increases with age. Interestingly, only the 5- to 10-year-old children displayed significant signal increases for the stream with low statistical regularities, suggesting an age-related decrease in sensitivity to more subtle statistical cues. Further, in a sample of 78 10-year-olds, we examined the impact of proficiency in a second language and level of pubertal development on learning-related signal increases, showing that the brain regions involved in language learning are influenced by both experiential and maturational factors.
doi:10.1111/j.1467-7687.2011.01075.x
PMCID: PMC3717169  PMID: 22010887
7.  Cracking the Language Code: Neural Mechanisms Underlying Speech Parsing 
Word segmentation, detecting word boundaries in continuous speech, is a critical aspect of language learning. Previous research in infants and adults demonstrated that a stream of speech can be readily segmented based solely on the statistical and speech cues afforded by the input. Using functional magnetic resonance imaging (fMRI), the neural substrate of word segmentation was examined on-line as participants listened to three streams of concatenated syllables, containing either statistical regularities alone, statistical regularities and speech cues, or no cues. Despite the participants’ inability to explicitly detect differences between the speech streams, neural activity differed significantly across conditions, with left-lateralized signal increases in temporal cortices observed only when participants listened to streams containing statistical regularities, particularly the stream containing speech cues. In a second fMRI study, designed to verify that word segmentation had implicitly taken place, participants listened to trisyllabic combinations that occurred with different frequencies in the streams of speech they just heard (“words,” 45 times; “partwords,” 15 times; “nonwords,” once). Reliably greater activity in left inferior and middle frontal gyri was observed when comparing words with partwords and, to a lesser extent, when comparing partwords with nonwords. Activity in these regions, taken to index the implicit detection of word boundaries, was positively correlated with participants’ rapid auditory processing skills. These findings provide a neural signature of on-line word segmentation in the mature brain and an initial model with which to study developmental changes in the neural architecture involved in processing speech cues during language learning.
doi:10.1523/JNEUROSCI.5501-05.2006
PMCID: PMC3713232  PMID: 16855090
fMRI; language; speech perception; word segmentation; statistical learning; auditory cortex; inferior frontal gyrus
8.  PET Imaging of Neuropathology in Tauopathies: Progressive Supranuclear Palsy 
Objective
Currently [F-18]FDDNP is the only PET imaging probe with the ability to visualize hyperphosphorylated tau fibrillar aggregates in living subjects. In this work, we evaluate in vivo [F-18]FDDNP labeling of brain neuropathology, primarily tau fibrillar aggregates, in patients with progressive supranuclear palsy (PSP), a human tauopathy usually lacking β-amyloid deposits.
Methods
Fifteen patients with PSP received [F-18]FDDNP PET scanning. [F-18]FDDNP distribution volume ratios (DVR), in reference to cerebellar gray matter, were determined for cortical and subcortical areas and compared with those of patients with Parkinson’s disease (PD) with short disease duration, and age-matched control subjects without neurodegenerative disorders.
Results
[F-18]FDDNP binding was present in subcortical areas (e.g., striatum, thalamus, subthalamic region, midbrain and cerebellar white matter) regardless of disease severity, with progressive subcortical and cortical involvement as disease severity increased. Brain patterns of [F-18]FDDNP binding were entirely consistent with the known pathology distribution for PSP. High midbrain and subthalamic region [F-18]FDDNP binding was distinctive for PSP subjects and separated them from controls and patients with PD.
Conclusions
These results provide evidence that [F-18]FDDNP is a sensitive in vivo PET imaging probe to map and quantify the dynamic regional localization of tau fibrillar aggregates in PSP. Furthermore, [F-18]FDDNP PET may provide a tool to detect changes in tau pathology distribution either associated with disease progression or as a treatment biomarker for future tau-specific therapies. Patterns of [F-18]FDDNP binding may also be useful in diagnosis early in disease presentation when clinical distinction among neurodegenerative disorders is often difficult.
doi:10.3233/JAD-130032
PMCID: PMC3674205  PMID: 23579330
Key-words: positron emission tomography; FDDNP; progressive supranuclear palsy; Parkinson’s disease; neuropathology; hyperphosphorylated tau aggregates; tauopathy
9.  The Myth of the Normal, Average Human Brain—The ICBM Experience: (1) Subject Screening and Eligibility 
NeuroImage  2008;44(3):914-922.
In the course of developing an atlas and reference system for the normal human brain throughout the human age span from structural and functional brain imaging data, the International Consortium for Brain Mapping (ICBM) developed a set of “normal” criteria for subject inclusion and the associated exclusion criteria. The approach was to minimize inclusion of subjects with any medical disorders that could affect brain structure or function. In the past two years, a group of 1,685 potential subjects responded to solicitation advertisements at one of the consortium sites (UCLA). Subjects were screened by a detailed telephone interview and then had an in-person history and physical examination. Of those who responded to the advertisement and considered themselves to be normal, only 31.6% (532 subjects) passed the telephone screening process. Of the 348 individuals who submitted to in-person history and physical examinations, only 51.7% passed these screening procedures. Thus, only 10.7% of those individuals who responded to the original advertisement qualified for imaging. The most frequent cause for exclusion in the second phase of subject screening was high blood pressure followed by abnormal signs on neurological examination. It is concluded that the majority of individuals who consider themselves normal by self-report are found not to be so by detailed historical interviews about underlying medical conditions and by thorough medical and neurological examinations. Recommendations are made with regard to the inclusion of subjects in brain imaging studies and the criteria used to select them.
doi:10.1016/j.neuroimage.2008.07.062
PMCID: PMC2651672  PMID: 18775497
10.  Superficially Located White Matter Structures Commonly Seen in the Human and the Macaque Brain with Diffusion Tensor Imaging 
Brain connectivity  2011;1(1):37-47.
The white matter of the brain consists of fiber tracts that connect different regions of the brain. Among these tracts, the intrahemispheric cortico-cortical connections are called association fibers. The U-fibers are short association fibers that connect adjacent gyri. These fibers were thought to work as part of the cortico-cortical networks to execute associative brain functions. However, their anatomy and functions have not been documented in detail for the human brain. In past studies, U-fibers have been characterized in the human brain with diffusion tensor imaging (DTI). However, the validity of such findings remains unclear. In this study, DTI of the macaque brain was performed, and the anatomy of U-fibers was compared with that of the human brain reported in a previous study. The macaque brain was chosen because it is the most commonly used animal model for exploring cognitive functions and the U-fibers of the macaque brain have been already identified by axonal tracing studies, which makes it an ideal system for confirming the DTI findings. Ten U-fibers found in the macaque brain were also identified in the human brain, with a similar organization and topology. The delineation of these species-conserved white matter structures may provide new options for understanding brain anatomy and function.
doi:10.1089/brain.2011.0005
PMCID: PMC3569096  PMID: 22432953
association fiber; blade; diffusion tensor imaging; macaque, U-fiber; white matter
11.  Facing puberty: associations between pubertal development and neural responses to affective facial displays 
Adolescence is marked by profound psychosocial and physiological changes. Although investigations into the interactions between these forces have begun to shed light on the neural correlates of affective processing during the transition to adolescence, relatively little is known about the relationship between pubertal development and emotion perception at the neural level. In the current longitudinal study, 45 neurotypical participants were shown affective facial displays while undergoing fMRI, at ages 10 and 13. Neural responses to emotional expressions at both time points were then correlated with a self-report measure of pubertal development, revealing positive associations with activity in amygdala, thalamus and visual cortical areas at age 10 that increased in magnitude and extent by age 13. At the latter time point, pubertal development was additionally correlated with enhanced responses to faces in temporal pole, ventrolateral prefrontal cortex (PFC) and dorsomedial PFC. Longitudinal comparisons revealed that the relationships between pubertal development and activity in the amygdala, hippocampus and temporal pole were significantly stronger during early adolescence than late childhood. These results suggest that pubertal development per se is linked to neural processing of socioemotional stimuli, particularly with respect to the integration of complex perceptual input and higher order cortical processing of affective content.
doi:10.1093/scan/nsr066
PMCID: PMC3252633  PMID: 22228752
adolescence; puberty; emotion; fMRI; amygdala; longitudinal
12.  Superficially Located White Matter Structures Commonly Seen in the Human and the Macaque Brain with Diffusion Tensor Imaging 
Brain Connectivity  2011;1(1):37-47.
Abstract
The white matter of the brain consists of fiber tracts that connect different regions of the brain. Among these tracts, the intrahemispheric cortico-cortical connections are called association fibers. The U-fibers are short association fibers that connect adjacent gyri. These fibers were thought to work as part of the cortico-cortical networks to execute associative brain functions. However, their anatomy and functions have not been documented in detail for the human brain. In past studies, U-fibers have been characterized in the human brain with diffusion tensor imaging (DTI). However, the validity of such findings remains unclear. In this study, DTI of the macaque brain was performed, and the anatomy of U-fibers was compared with that of the human brain reported in a previous study. The macaque brain was chosen because it is the most commonly used animal model for exploring cognitive functions and the U-fibers of the macaque brain have been already identified by axonal tracing studies, which makes it an ideal system for confirming the DTI findings. Ten U-fibers found in the macaque brain were also identified in the human brain, with a similar organization and topology. The delineation of these species-conserved white matter structures may provide new options for understanding brain anatomy and function.
doi:10.1089/brain.2011.0005
PMCID: PMC3569096  PMID: 22432953
association fiber; blade; diffusion tensor imaging; macaque, U-fiber; white matter
13.  The Neural Basis of Speech Parsing in Children and Adults 
Developmental science  2010;13(2):385-406.
Word segmentation, detecting word boundaries in continuous speech, is a fundamental aspect of language learning that can occur solely by the computation of statistical and speech cues. Fifty-four children underwent functional magnetic resonance imaging (fMRI) while listening to three streams of concatenated syllables, which contained either high statistical regularities, high statistical regularities and speech cues, or no easily-detectable cues. Significant signal increases over time in temporal cortices suggest that children utilized the cues to implicitly segment the speech streams. This was confirmed by the findings of a second fMRI run where children displayed reliably greater activity in left inferior frontal gyrus when listening to ‘words’ that occurred more frequently in the streams of speech they just heard. Finally, comparisons between activity observed in these children vs. previously-studied adults indicate significant developmental changes in the neural substrate of speech parsing.
doi:10.1111/j.1467-7687.2009.00895.x
PMCID: PMC3229831  PMID: 20136936
fMRI; language; development; speech perception; word segmentation; statistical learning
14.  Atlas-Guided Tract Reconstruction for Automated and Comprehensive Examination of the White Matter Anatomy 
NeuroImage  2010;52(4):1289-1301.
Tractography based on diffusion tensor imaging (DTI) is widely used to quantitatively analyze the status of the white matter anatomy in a tract-specific manner in many types of diseases. This approach, however, involves subjective judgment in the tract-editing process to extract only the tracts of interest. This process, usually performed by manual delineation of regions of interest, is also time-consuming, and certain tracts, especially the short cortico-cortical association fibers, are difficult to reconstruct. In this paper, we propose an automated approach for reconstruction of a large number of white matter tracts. In this approach, existing anatomical knowledge about tract trajectories (called the Template ROI Set or TRS) were stored in our DTI-based brain atlas with 130 three-dimensional anatomical segmentations, which were warped non-linearly to individual DTI data. We examined the degree of matching with manual results for selected fibers. We established 30 TRSs to reconstruct 30 prominent and previously well-described fibers. In addition, TRSs were developed to delineate 29 short association fibers that were found in all normal subjects examined in this paper (N=20). Probabilistic maps of the 59 tract trajectories were created from the normal subjects and were incorporated into our image analysis tool for automated tract-specific quantification.
doi:10.1016/j.neuroimage.2010.05.049
PMCID: PMC2910162  PMID: 20570617
human; white matter; automated; atlas; association fiber; tractography; magnetic resonance imaging; diffusion tensor
15.  Offering to Share: How to Put Heads Together in Autism Neuroimaging 
Data sharing in autism neuroimaging presents scientific, technical, and social obstacles. We outline the desiderata for a data-sharing scheme that combines imaging with other measures of phenotype and with genetics, defines requirements for comparability of derived data and recommendations for raw data, outlines a core protocol including multispectral structural and diffusion-tensor imaging and optional extensions, provides for the collection of prospective, confound-free normative data, and extends sharing and collaborative development not only to data but to the analytical tools and methods applied to these data. A theme in these requirements is the need to preserve creative approaches and risk-taking within individual laboratories at the same time as common standards are provided for these laboratories to build on.
doi:10.1007/s10803-006-0352-2
PMCID: PMC3076291  PMID: 17347882
Imaging; MRI; PET; Morphometry; Segmentation; Data sharing
16.  Alterations in Functional Activation in Euthymic Bipolar Disorder and Schizophrenia During a Working Memory Task 
Human brain mapping  2009;30(12):3958-3969.
Dysfunctions in prefrontal cortical networks are thought to underlie working memory (WM) impairments consistently observed in both subjects with bipolar disorder and schizophrenia. It remains unclear, however, whether patterns of WM-related hemodynamic responses are similar in bipolar and schizophrenia subjects compared to controls. We used fMRI to investigate differences in blood-oxygen-level-dependent (BOLD) activation during a WM task in 21 euthymic bipolar I patients, 20 schizophrenia patients, and 38 healthy controls. Subjects were presented with four stimuli (abstract designs) followed by a fifth stimulus, and required to recall whether the last stimulus was among the four presented previously. Task-related brain activity was compared within and across groups. All groups activated prefrontal cortex (PFC), primary and supplementary motor cortex, and visual cortex during the WM task. There were no significant differences in PFC activation between controls and euthymic bipolar subjects, but controls exhibited significantly increased activation (cluster-corrected P<0.05) compared to schizophrenia patients in prefrontal regions including dorso-lateral prefrontal cortex (DLPFC). While the bipolar group exhibited intermediate percent signal change in a functionally-defined DLPFC region of interest with respect to the schizophrenia and control groups, effects remained significant only between schizophrenia patients and controls. Schizophrenia and bipolar disorder may share some behavioral, diagnostic, and genetic features. Differences in the patterns of WM-related brain activity across groups, however, suggest some diagnostic specificity. Both patient groups showed some regional task-related hypoactivation compared to controls across the brain. Within DLPFC specifically, schizophrenia patients exhibited more severe WM-related dysfunction than bipolar subjects.
doi:10.1002/hbm.20820
PMCID: PMC2787769  PMID: 19449330
bipolar; schizophrenia; working memory; executive function; fMRI; dorsolateral prefrontal cortex
17.  Neural correlates of social exclusion during adolescence: understanding the distress of peer rejection 
Developmental research has demonstrated the harmful effects of peer rejection during adolescence; however, the neural mechanisms responsible for this salience remain unexplored. In this study, 23 adolescents were excluded during a ball-tossing game in which they believed they were playing with two other adolescents during an fMRI scan; in reality, participants played with a preset computer program. Afterwards, participants reported their exclusion-related distress and rejection sensitivity, and parents reported participants’ interpersonal competence. Similar to findings in adults, during social exclusion adolescents displayed insular activity that was positively related to self-reported distress, and right ventrolateral prefrontal activity that was negatively related to self-reported distress. Findings unique to adolescents indicated that activity in the subgenual anterior cingulate cortex (subACC) related to greater distress, and that activity in the ventral striatum related to less distress and appeared to play a role in regulating activity in the subACC and other regions involved in emotional distress. Finally, adolescents with higher rejection sensitivity and interpersonal competence scores displayed greater neural evidence of emotional distress, and adolescents with higher interpersonal competence scores also displayed greater neural evidence of regulation, perhaps suggesting that adolescents who are vigilant regarding peer acceptance may be most sensitive to rejection experiences.
doi:10.1093/scan/nsp007
PMCID: PMC2686232  PMID: 19470528
peer rejection; adolescence; functional magnetic resonance imaging
18.  Seizures and Hemiparesis in a Young Woman 24 Years After Treatment of Astrocytoma 
Western Journal of Medicine  1989;150(2):180-186.
An edited transcript of Neurology Grand Rounds held at the University of California, Los Angeles, Medical Center on January 27, 1988. John Mazziotta, MD, PhD, Professor of Neurology and Radiology, is the coordinator of these conferences. This conference was edited by Harry V. Vinters, MD.
Images
PMCID: PMC1026331  PMID: 2728438
19.  PATTERNS OF BRAIN ACTIVATION IN PEOPLE AT RISK FOR ALZHEIMER’S DISEASE 
The New England journal of medicine  2000;343(7):450-456.
Background
The ε4 allele of the apolipoprotein E gene (APOE) is the chief known genetic risk factor for Alzheimer’s disease, the most common cause of dementia late in life. To determine the relation between brain responses to tasks requiring memory and the genetic risk of Alzheimer’s disease, we performed APOE genotyping and functional magnetic resonance imaging (MRI) of the brain in older persons with intact cognition.
Methods
We studied 30 subjects (age, 47 to 82 years) who were neurologically normal, of whom 16 were carriers of the APOE ε4 allele and 14 were homozygous for the APOE ε3 allele. The mean age and level of education were similar in the two groups. Patterns of brain activation during functional MRI scanning were determined while subjects memorized and recalled unrelated pairs of words and while subjects rested between such periods. Memory was reassessed in 14 subjects two years later.
Results
Both the magnitude and the extent of brain activation during memory-activation tasks in regions affected by Alzheimer’s disease, including the left hippocampal, parietal, and prefrontal regions, were greater among the carriers of the APOE ε4 allele than among the carriers of the APOE ε3 allele. During periods of recall, the carriers of the APOE ε4 allele had a greater average increase in signal intensity in the hippocampal region (1.03 percent vs. 0.62 percent, P<0.001) and a greater mean (±SD) number of activated regions throughout the brain (15.9±6.2 vs. 9.4±5.5, P=0.005) than did carriers of the APOE ε3 allele. Longitudinal assessment after two years indicated that the degree of base-line brain activation correlated with degree of decline in memory.
Conclusions
Patterns of brain activation during tasks requiring memory differ depending on the genetic risk of Alzheimer’s disease and may predict a subsequent decline in memory.
doi:10.1056/NEJM200008173430701
PMCID: PMC2831477  PMID: 10944562
20.  Engagement of Fusiform Cortex and Disengagement of Lateral Occipital Cortex in the Acquisition of Radiological Expertise 
Cerebral Cortex (New York, NY)  2009;19(11):2746-2754.
The human visual pathways that are specialized for object recognition stretch from lateral occipital cortex (LO) to the ventral surface of the temporal lobe, including the fusiform gyrus. Plasticity in these pathways supports the acquisition of visual expertise, but precisely how training affects the different regions remains unclear. We used functional magnetic resonance imaging to measure neural activity in both LO and the fusiform gyrus in radiologists as they detected abnormalities in chest radiographs. Activity in the right fusiform face area (FFA) correlated with visual expertise, measured as behavioral performance during scanning. In contrast, activity in left LO correlated negatively with expertise, and the amount of LO that responded to radiographs was smaller in experts than in novices. Activity in the FFA and LO correlated negatively in experts, whereas in novices, the 2 regions showed no stable relationship. Together, these results suggest that the FFA becomes more engaged and left LO less engaged in interpreting radiographic images over the course of training. Achieving expert visual performance may involve suppressing existing neural representations while simultaneously developing others.
doi:10.1093/cercor/bhp051
PMCID: PMC2758686  PMID: 19321653
diagnosis; expert; FFA; radiology; vision
21.  Grasping the Intentions of Others with One's Own Mirror Neuron System 
PLoS Biology  2005;3(3):e79.
Understanding the intentions of others while watching their actions is a fundamental building block of social behavior. The neural and functional mechanisms underlying this ability are still poorly understood. To investigate these mechanisms we used functional magnetic resonance imaging. Twenty-three subjects watched three kinds of stimuli: grasping hand actions without a context, context only (scenes containing objects), and grasping hand actions performed in two different contexts. In the latter condition the context suggested the intention associated with the grasping action (either drinking or cleaning). Actions embedded in contexts, compared with the other two conditions, yielded a significant signal increase in the posterior part of the inferior frontal gyrus and the adjacent sector of the ventral premotor cortex where hand actions are represented. Thus, premotor mirror neuron areas—areas active during the execution and the observation of an action—previously thought to be involved only in action recognition are actually also involved in understanding the intentions of others. To ascribe an intention is to infer a forthcoming new goal, and this is an operation that the motor system does automatically.
Functional magnetic resonance imaging is used to explore the responses of premotor cortical areas to observing the actions of others
doi:10.1371/journal.pbio.0030079
PMCID: PMC1044835  PMID: 15736981

Results 1-21 (21)