The impact of anxiety-inducing distraction on cognitive performance: a combined brain imaging and personality investigation.

BACKGROUND: Previous investigations revealed that the impact of task-irrelevant emotional distraction on ongoing goal-oriented cognitive processing is linked to opposite patterns of activation in emotional and perceptual vs. cognitive control/executive brain regions. However, little is known about the role of individual variations in these responses. The present study investigated the effect of trait anxiety on the neural responses mediating the impact of transient anxiety-inducing task-irrelevant distraction on cognitive performance, and on the neural correlates of coping with such distraction. We investigated whether activity in the brain regions sensitive to emotional distraction would show dissociable patterns of co-variation with measures indexing individual variations in trait anxiety and cognitive performance. METHODOLOGY/PRINCIPAL FINDINGS: Event-related fMRI data, recorded while healthy female participants performed a delayed-response working memory (WM) task with distraction, were investigated in conjunction with behavioural measures that assessed individual variations in both trait anxiety and WM performance. Consistent with increased sensitivity to emotional cues in high anxiety, specific perceptual areas (fusiform gyrus--FG) exhibited increased activity that was positively correlated with trait anxiety and negatively correlated with WM performance, whereas specific executive regions (right lateral prefrontal cortex--PFC) exhibited decreased activity that was negatively correlated with trait anxiety. The study also identified a role of the medial and left lateral PFC in coping with distraction, as opposed to reflecting a detrimental impact of emotional distraction. CONCLUSIONS: These findings provide initial evidence concerning the neural mechanisms sensitive to individual variations in trait anxiety and WM performance, which dissociate the detrimental impact of emotion distraction and the engagement of mechanisms to cope with distracting emotions. Our study sheds light on the neural correlates of emotion-cognition interactions in normal behaviour, which has implications for understanding factors that may influence susceptibility to affective disorders, in general, and to anxiety disorders, in particular.

ENIGMA and the individual: Predicting factors that affect the brain in 35 countries worldwide.

In this review, we discuss recent work by the ENIGMA Consortium (http://enigma.ini.usc.edu) - a global alliance of over 500 scientists spread across 200 institutions in 35 countries collectively analyzing brain imaging, clinical, and genetic data. Initially formed to detect genetic influences on brain measures, ENIGMA has grown to over 30 working groups studying 12 major brain diseases by pooling and comparing brain data. In some of the largest neuroimaging studies to date - of schizophrenia and major depression - ENIGMA has found replicable disease effects on the brain that are consistent worldwide, as well as factors that modulate disease effects. In partnership with other consortia including ADNI, CHARGE, IMAGEN and others(1), ENIGMA's genomic screens - now numbering over 30,000 MRI scans - have revealed at least 8 genetic loci that affect brain volumes. Downstream of gene findings, ENIGMA has revealed how these individual variants - and genetic variants in general - may affect both the brain and risk for a range of diseases. The ENIGMA consortium is discovering factors that consistently affect brain structure and function that will serve as future predictors linking individual brain scans and genomic data. It is generating vast pools of normative data on brain measures - from tens of thousands of people - that may help detect deviations from normal development or aging in specific groups of subjects. We discuss challenges and opportunities in applying these predictors to individual subjects and new cohorts, as well as lessons we have learned in ENIGMA's efforts so far.

Introduction of novel video-based tasks to clinical fMRI: Comparing traditional fMRI tasks with novel video-based tasks for mapping brain language areas

Recently, blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) has become a routine clinical procedure for localization of language and motor brain regions and has been replacing more invasive preoperative procedures. However, the fMRI results from these tasks are not always reproducible even from the same patient. Evaluating the reproducibility of language and speech mapping is especially complicated due to the complex brain circuitry that may become activated during the functional task. Non-language areas such as sensory, attention, decision-making, and motor brain regions may also be activated in addition to the specific language regions during a traditional sentence-completion task. In this study, I test a new approach, which utilizes 4-minute video-based tasks, to map language and speech brain regions for patients undergoing brain surgery. Results from 35 subjects have shown that the video-based task activates Wernicke’s area, as well as Broca’s area in most subjects. The computed laterality indices, which indicate the dominant hemisphere from that functional task, have indicated left dominance from the video-based tasks. This study has shown that the video-based task may be an alternative method for localization of language and speech brain regions for patients who are unable to complete the sentence-completion task.

Do You Want to Hear the Bad News? The Value of Diagnostic Tests for Alzheimer's Disease.

OBJECTIVE: The diagnosis of Alzheimer's disease (AD) remains difficult. Lack of diagnostic certainty or possible distress related to a positive result from diagnostic testing could limit the application of new testing technologies. The objective of this paper is to quantify respondents' preferences for obtaining AD diagnostic tests and to estimate the perceived value of AD test information. METHODS: Discrete-choice experiment and contingent-valuation questions were administered to respondents in Germany and the United Kingdom. Choice data were analyzed by using random-parameters logit. A probit model characterized respondents who were not willing to take a test. RESULTS: Most respondents indicated a positive value for AD diagnostic test information. Respondents who indicated an interest in testing preferred brain imaging without the use of radioactive markers. German respondents had relatively lower money-equivalent values for test features compared with respondents in the United Kingdom. CONCLUSIONS: Respondents preferred less invasive diagnostic procedures and tests with higher accuracy and expressed a willingness to pay up to €700 to receive a less invasive test with the highest accuracy.

Photoacoustic tomography: principles and advances.

Photoacoustic tomography (PAT) is an emerging imaging modality that shows great potential for preclinical research and clinical practice. As a hybrid technique, PAT is based on the acoustic detection of optical absorption from either endogenous chromophores, such as oxy-hemoglobin and deoxy-hemoglobin, or exogenous contrast agents, such as organic dyes and nanoparticles. Because ultrasound scatters much less than light in tissue, PAT generates high-resolution images in both the optical ballistic and diffusive regimes. Over the past decade, the photoacoustic technique has been evolving rapidly, leading to a variety of exciting discoveries and applications. This review covers the basic principles of PAT and its different implementations. Strengths of PAT are highlighted, along with the most recent imaging results.

Improved delineation of short cortical association fibers and gray/white matter boundary using whole-brain three-dimensional diffusion tensor imaging at submillimeter spatial resolution.

Recent emergence of human connectome imaging has led to a high demand on angular and spatial resolutions for diffusion magnetic resonance imaging (MRI). While there have been significant growths in high angular resolution diffusion imaging, the improvement in spatial resolution is still limited due to a number of technical challenges, such as the low signal-to-noise ratio and high motion artifacts. As a result, the benefit of a high spatial resolution in the whole-brain connectome imaging has not been fully evaluated in vivo. In this brief report, the impact of spatial resolution was assessed in a newly acquired whole-brain three-dimensional diffusion tensor imaging data set with an isotropic spatial resolution of 0.85 mm. It was found that the delineation of short cortical association fibers is drastically improved as well as the definition of fiber pathway endings into the gray/white matter boundary-both of which will help construct a more accurate structural map of the human brain connectome.

High-field FMRI reveals brain activation patterns underlying saccade execution in the human superior colliculus.

BACKGROUND: The superior colliculus (SC) has been shown to play a crucial role in the initiation and coordination of eye- and head-movements. The knowledge about the function of this structure is mainly based on single-unit recordings in animals with relatively few neuroimaging studies investigating eye-movement related brain activity in humans. METHODOLOGY/PRINCIPAL FINDINGS: The present study employed high-field (7 Tesla) functional magnetic resonance imaging (fMRI) to investigate SC responses during endogenously cued saccades in humans. In response to centrally presented instructional cues, subjects either performed saccades away from (centrifugal) or towards (centripetal) the center of straight gaze or maintained fixation at the center position. Compared to central fixation, the execution of saccades elicited hemodynamic activity within a network of cortical and subcortical areas that included the SC, lateral geniculate nucleus (LGN), occipital cortex, striatum, and the pulvinar. CONCLUSIONS/SIGNIFICANCE: Activity in the SC was enhanced contralateral to the direction of the saccade (i.e., greater activity in the right as compared to left SC during leftward saccades and vice versa) during both centrifugal and centripetal saccades, thereby demonstrating that the contralateral predominance for saccade execution that has been shown to exist in animals is also present in the human SC. In addition, centrifugal saccades elicited greater activity in the SC than did centripetal saccades, while also being accompanied by an enhanced deactivation within the prefrontal default-mode network. This pattern of brain activity might reflect the reduced processing effort required to move the eyes toward as compared to away from the center of straight gaze, a position that might serve as a spatial baseline in which the retinotopic and craniotopic reference frames are aligned.

Variability in frontotemporal brain structure: the importance of recruitment of African Americans in neuroscience research.

BACKGROUND: Variation in brain structure is both genetically and environmentally influenced. The question about potential differences in brain anatomy across populations of differing race and ethnicity remains a controversial issue. There are few studies specifically examining racial or ethnic differences and also few studies that test for race-related differences in context of other neuropsychiatric research, possibly due to the underrepresentation of ethnic minorities in clinical research. It is within this context that we conducted a secondary data analysis examining volumetric MRI data from healthy participants and compared the volumes of the amygdala, hippocampus, lateral ventricles, caudate nucleus, orbitofrontal cortex (OFC) and total cerebral volume between Caucasian and African-American participants. We discuss the importance of this finding in context of neuroimaging methodology, but also the need for improved recruitment of African Americans in clinical research and its broader implications for a better understanding of the neural basis of neuropsychiatric disorders. METHODOLOGY/PRINCIPAL FINDINGS: This was a case control study in the setting of an academic medical center outpatient service. Participants consisted of 44 Caucasians and 33 ethnic minorities. The following volumetric data were obtained: amygdala, hippocampus, lateral ventricles, caudate nucleus, orbitofrontal cortex (OFC) and total cerebrum. Each participant completed a 1.5 T magnetic resonance imaging (MRI). Our primary finding in analyses of brain subregions was that when compared to Caucasians, African Americans exhibited larger left OFC volumes (F (1,68) = 7.50, p = 0.008). CONCLUSIONS: The biological implications of our findings are unclear as we do not know what factors may be contributing to these observed differences. However, this study raises several questions that have important implications for the future of neuropsychiatric research.

Functional parcellation of attentional control regions of the brain.

Recently, a number of investigators have examined the neural loci of psychological processes enabling the control of visual spatial attention using cued-attention paradigms in combination with event-related functional magnetic resonance imaging. Findings from these studies have provided strong evidence for the involvement of a fronto-parietal network in attentional control. In the present study, we build upon this previous work to further investigate these attentional control systems. In particular, we employed additional controls for nonattentional sensory and interpretative aspects of cue processing to determine whether distinct regions in the fronto-parietal network are involved in different aspects of cue processing, such as cue-symbol interpretation and attentional orienting. In addition, we used shorter cue-target intervals that were closer to those used in the behavioral and event-related potential cueing literatures. Twenty participants performed a cued spatial attention task while brain activity was recorded with functional magnetic resonance imaging. We found functional specialization for different aspects of cue processing in the lateral and medial subregions of the frontal and parietal cortex. In particular, the medial subregions were more specific to the orienting of visual spatial attention, while the lateral subregions were associated with more general aspects of cue processing, such as cue-symbol interpretation. Additional cue-related effects included differential activations in midline frontal regions and pretarget enhancements in the thalamus and early visual cortical areas.

Functional imaging of numerical processing in adults and 4-y-old children.

Adult humans, infants, pre-school children, and non-human animals appear to share a system of approximate numerical processing for non-symbolic stimuli such as arrays of dots or sequences of tones. Behavioral studies of adult humans implicate a link between these non-symbolic numerical abilities and symbolic numerical processing (e.g., similar distance effects in accuracy and reaction-time for arrays of dots and Arabic numerals). However, neuroimaging studies have remained inconclusive on the neural basis of this link. The intraparietal sulcus (IPS) is known to respond selectively to symbolic numerical stimuli such as Arabic numerals. Recent studies, however, have arrived at conflicting conclusions regarding the role of the IPS in processing non-symbolic, numerosity arrays in adulthood, and very little is known about the brain basis of numerical processing early in development. Addressing the question of whether there is an early-developing neural basis for abstract numerical processing is essential for understanding the cognitive origins of our uniquely human capacity for math and science. Using functional magnetic resonance imaging (fMRI) at 4-Tesla and an event-related fMRI adaptation paradigm, we found that adults showed a greater IPS response to visual arrays that deviated from standard stimuli in their number of elements, than to stimuli that deviated in local element shape. These results support previous claims that there is a neurophysiological link between non-symbolic and symbolic numerical processing in adulthood. In parallel, we tested 4-y-old children with the same fMRI adaptation paradigm as adults to determine whether the neural locus of non-symbolic numerical activity in adults shows continuity in function over development. We found that the IPS responded to numerical deviants similarly in 4-y-old children and adults. To our knowledge, this is the first evidence that the neural locus of adult numerical cognition takes form early in development, prior to sophisticated symbolic numerical experience. More broadly, this is also, to our knowledge, the first cognitive fMRI study to test healthy children as young as 4 y, providing new insights into the neurophysiology of human cognitive development.

Brain activity during episodic retrieval of autobiographical and laboratory events: an fMRI study using a novel photo paradigm.

Functional neuroimaging studies of episodic memory retrieval generally measure brain activity while participants remember items encountered in the laboratory ("controlled laboratory condition") or events from their own life ("open autobiographical condition"). Differences in activation between these conditions may reflect differences in retrieval processes, memory remoteness, emotional content, retrieval success, self-referential processing, visual/spatial memory, and recollection. To clarify the nature of these differences, a functional MRI study was conducted using a novel "photo paradigm," which allows greater control over the autobiographical condition, including a measure of retrieval accuracy. Undergraduate students took photos in specified campus locations ("controlled autobiographical condition"), viewed in the laboratory similar photos taken by other participants (controlled laboratory condition), and were then scanned while recognizing the two kinds of photos. Both conditions activated a common episodic memory network that included medial temporal and prefrontal regions. Compared with the controlled laboratory condition, the controlled autobiographical condition elicited greater activity in regions associated with self-referential processing (medial prefrontal cortex), visual/spatial memory (visual and parahippocampal regions), and recollection (hippocampus). The photo paradigm provides a way of investigating the functional neuroanatomy of real-life episodic memory under rigorous experimental control.

Activation in mesolimbic and visuospatial neural circuits elicited by smoking cues: evidence from functional magnetic resonance imaging.

OBJECTIVE: The authors sought to increase understanding of the brain mechanisms involved in cigarette addiction by identifying neural substrates modulated by visual smoking cues in nicotine-deprived smokers. METHOD: Event-related functional magnetic resonance imaging (fMRI) was used to detect brain activation after exposure to smoking-related images in a group of nicotine-deprived smokers and a nonsmoking comparison group. Subjects viewed a pseudo-random sequence of smoking images, neutral nonsmoking images, and rare targets (photographs of animals). Subjects pressed a button whenever a rare target appeared. RESULTS: In smokers, the fMRI signal was greater after exposure to smoking-related images than after exposure to neutral images in mesolimbic dopamine reward circuits known to be activated by addictive drugs (right posterior amygdala, posterior hippocampus, ventral tegmental area, and medial thalamus) as well as in areas related to visuospatial attention (bilateral prefrontal and parietal cortex and right fusiform gyrus). In nonsmokers, no significant differences in fMRI signal following exposure to smoking-related and neutral images were detected. In most regions studied, both subject groups showed greater activation following presentation of rare target images than after exposure to neutral images. CONCLUSIONS: In nicotine-deprived smokers, both reward and attention circuits were activated by exposure to smoking-related images. Smoking cues are processed like rare targets in that they activate attentional regions. These cues are also processed like addictive drugs in that they activate mesolimbic reward regions.

A Dynamic Directional Model for Effective Brain Connectivity using Electrocorticographic (ECoG) Time Series.

We introduce a dynamic directional model (DDM) for studying brain effective connectivity based on intracranial electrocorticographic (ECoG) time series. The DDM consists of two parts: a set of differential equations describing neuronal activity of brain components (state equations), and observation equations linking the underlying neuronal states to observed data. When applied to functional MRI or EEG data, DDMs usually have complex formulations and thus can accommodate only a few regions, due to limitations in spatial resolution and/or temporal resolution of these imaging modalities. In contrast, we formulate our model in the context of ECoG data. The combined high temporal and spatial resolution of ECoG data result in a much simpler DDM, allowing investigation of complex connections between many regions. To identify functionally segregated sub-networks, a form of biologically economical brain networks, we propose the Potts model for the DDM parameters. The neuronal states of brain components are represented by cubic spline bases and the parameters are estimated by minimizing a log-likelihood criterion that combines the state and observation equations. The Potts model is converted to the Potts penalty in the penalized regression approach to achieve sparsity in parameter estimation, for which a fast iterative algorithm is developed. The methods are applied to an auditory ECoG dataset.

A Diffusion MRI Tractography Connectome of the Mouse Brain and Comparison with Neuronal Tracer Data.

Interest in structural brain connectivity has grown with the understanding that abnormal neural connections may play a role in neurologic and psychiatric diseases. Small animal connectivity mapping techniques are particularly important for identifying aberrant connectivity in disease models. Diffusion magnetic resonance imaging tractography can provide nondestructive, 3D, brain-wide connectivity maps, but has historically been limited by low spatial resolution, low signal-to-noise ratio, and the difficulty in estimating multiple fiber orientations within a single image voxel. Small animal diffusion tractography can be substantially improved through the combination of ex vivo MRI with exogenous contrast agents, advanced diffusion acquisition and reconstruction techniques, and probabilistic fiber tracking. Here, we present a comprehensive, probabilistic tractography connectome of the mouse brain at microscopic resolution, and a comparison of these data with a neuronal tracer-based connectivity data from the Allen Brain Atlas. This work serves as a reference database for future tractography studies in the mouse brain, and demonstrates the fundamental differences between tractography and neuronal tracer data.

Localization of Metal Electrodes in the Intact Rat Brain Using Registration of 3D Microcomputed Tomography Images to a Magnetic Resonance Histology Atlas.

Simultaneous neural recordings taken from multiple areas of the rodent brain are garnering growing interest due to the insight they can provide about spatially distributed neural circuitry. The promise of such recordings has inspired great progress in methods for surgically implanting large numbers of metal electrodes into intact rodent brains. However, methods for localizing the precise location of these electrodes have remained severely lacking. Traditional histological techniques that require slicing and staining of physical brain tissue are cumbersome, and become increasingly impractical as the number of implanted electrodes increases. Here we solve these problems by describing a method that registers 3-D computerized tomography (CT) images of intact rat brains implanted with metal electrode bundles to a Magnetic Resonance Imaging Histology (MRH) Atlas. Our method allows accurate visualization of each electrode bundle's trajectory and location without removing the electrodes from the brain or surgically implanting external markers. In addition, unlike physical brain slices, once the 3D images of the electrode bundles and the MRH atlas are registered, it is possible to verify electrode placements from many angles by "re-slicing" the images along different planes of view. Further, our method can be fully automated and easily scaled to applications with large numbers of specimens. Our digital imaging approach to efficiently localizing metal electrodes offers a substantial addition to currently available methods, which, in turn, may help accelerate the rate at which insights are gleaned from rodent network neuroscience.