A current limitation for imaging of brain function is the potential confound of anatomical differences or registration error, which may manifest via apparent functional "activation" for between-subject analyses. With respect to functional activations, underlying tissue mismatches can be regarded as a nuisance variable. We propose adding the probability of gray matter at a given voxel as a covariate (nuisance variable) in the analysis of voxelwise multisubject functional data using standard statistical techniques. A method is presented to assess the extent to which a functional activation can reliably be explained by underlying anatomical differences, and simultaneously, to assess the component of the functional activation which cannot be attributed to anatomical difference and thus is likely due to functional difference alone. Extension of the method to other intermodal imaging applications is discussed. Two exemplary data sets, one PET and one fMRI, are used to demonstrate the implementation and utility of this method, which apportions the relative contributions of anatomy and function for an apparent functional activation. The examples show two distinct types of results. First, a so-called functional activation may actually be caused by a systematic anatomical difference which, when modeled, diminishes the functional effect. In the second result type, including the anatomical differences in the model can account for a large component of otherwise unmodeled variance, yielding an increase in the functional effect cluster size and/or magnitude. In either case, ignoring the readily available structural information can lead to misinterpretation of functional results.
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Based on previous findings in humans and rhesus monkeys suggesting that diazepam has asymmetrical effects on frontal lobe activity and other literature supporting a role for the benzodiazepine system in the mediation of individual differences in anxiety and fearfulness, the relation between asymmetrical changes in scalp-recorded regional brain activity in response to diazepam and the temperamental dimension of behavioral inhibition indexed by freezing time in 9 rhesus monkeys was examined. Animals showed greater relative left-sided frontal activation in response to diazepam compared with the preceding baseline. The magnitude of this shift was strongly correlated with an aggregate measure of freezing time (r = .82). The implications of these findings for understanding the role of regional differences in the benzodiazepine system in mediating individual differences in fearfulness are discussed.
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Baseline resting electroencephalogram activity was recorded with 3 different reference montages from 15 clinically depressed and 13 control subjects. Power in all frequency bands was extracted by fast Fourier transformation. There was a significant Group X Hemisphere interaction in the mid-frontal region, for the alpha band power only. Depressed subjects had less left-sided activation (i.e., more alpha activity) than did normal control subjects. This pattern of diminished left-sided frontal activation is interpreted as indicating a deficit in approach mechanisms in depressed subjects.
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Social contact promotes enhanced health and well-being, likely as a function of the social regulation of emotional responding in the face of various life stressors. For this functional magnetic resonance imaging (fMRI) study, 16 married women were subjected to the threat of electric shock while holding their husband's hand, the hand of an anonymous male experimenter, or no hand at all. Results indicated a pervasive attenuation of activation in the neural systems supporting emotional and behavioral threat responses when the women held their husband's hand. A more limited attenuation of activation in these systems occurred when they held the hand of a stranger. Most strikingly, the effects of spousal hand-holding on neural threat responses varied as a function of marital quality, with higher marital quality predicting less threat-related neural activation in the right anterior insula, superior frontal gyrus, and hypothalamus during spousal, but not stranger, hand-holding.
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Autism is a neurodevelopmental disorder affecting behavioral and social cognition, but there is little understanding about the link between the functional deficit and its underlying neuroanatomy. We applied a 2D version of voxel-based morphometry (VBM) in differentiating the white matter concentration of the corpus callosum for the group of 16 high functioning autistic and 12 normal subjects. Using the white matter density as an index for neural connectivity, autism is shown to exhibit less white matter concentration in the region of the genu, rostrum, and splenium removing the effect of age based on the general linear model (GLM) framework. Further, it is shown that the less white matter concentration in the corpus callosum in autism is due to hypoplasia rather than atrophy.
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In order to gain a deeper understanding of the mindfulness construct and the mental health benefits associated with mindfulness-based programmes, the relation between mindfulness and its proposed core component attention was studied. Buddhist and Western mindfulness meditators were compared with non-meditators on tasks of sustained (SART) and executive (the Stroop Task) attention. Relations between self-reported mindfulness (FFMQ) and sustained and executive attention were also analysed. No significant differences were found between meditators and non-meditators either in sustained or executive attention. High scores on the FFMQ total scale and on Describe were related to fewer SART errors. High scores on Describe were also related to low Stroop interference. Mindfulness meditators may have an increased awareness of internal processes and the ability to quickly attend to them but this type of refined attentional ability does not seem to be related to performance on attention tests requiring responses to external targets.
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The role of the amygdala in major depression was investigated. Resting regional cerebral metabolic rate (rCMRglu) was measured with [18F]fluorodeoxyglucose positron emission tomography (PET) in two samples of subjects using two different PET cameras. The samples consisted of 10 and 17 medication-free depressives and 11 and 13 controls, respectively. Using coregistration of PET and magnetic resonance images, regions were individually delineated for the amygdala and thalamus, the latter of which was used as a control region. Within the depressed groups, right amygdalar rCMRglu was positively correlated with negative affect. Thalamic rCMRglu was not related to negative affect, and amygdalar rCMRglu accounted for a significant portion of variance in depressives' negative affect scores over and above the contribution of thalamic rCMRglu.
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<p>Mindfulness-based approaches are among the most innovative and interesting new approaches to mental health treatment. Mindfulness refers to patients developing an "awareness of present experience with acceptance." Interest in them is widespread, with presentations and workshops drawing large audiences all over the US and many other countries. This book provides a comprehensive introduction to the best-researched mindfulness-based treatments. It emphasizes detailed clinical illustration providing a close-up view of how these treatments are conducted, the skills required of therapists, and how they work. The book also has a solid foundation in theory and research and shows clearly how these treatments can be understood using accepted psychological principles and concepts. The evidence base for these treatments is concisely reviewed.* Comprehensive introduction to the best-researched mindfulness-based treatments* Covers wide range of problems & disorders (anxiety, depression, eating, psychosis, personality disorders, stress, pain, relationship problems, etc)* Discusses a wide range of populations (children, adolescents, older adults, couples)* Includes wide range of settings (outpatient, inpatient, medical, mental health, workplace)* Clinically rich, illustrative case study in every chapter* International perspectives represented (authors from US, Canada, Britain, Sweden)</p>
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Studies have suggested that the default mode network is active during mind wandering, which is often experienced intermittently during sustained attention tasks. Conversely, an anticorrelated task-positive network is thought to subserve various forms of attentional processing. Understanding how these two systems work together is central for understanding many forms of optimal and sub-optimal task performance. Here we present a basic model of naturalistic cognitive fluctuations between mind wandering and attentional states derived from the practice of focused attention meditation. This model proposes four intervals in a cognitive cycle: mind wandering, awareness of mind wandering, shifting of attention, and sustained attention. People who train in this style of meditation cultivate their abilities to monitor cognitive processes related to attention and distraction, making them well suited to report on these mental events. Fourteen meditation practitioners performed breath-focused meditation while undergoing fMRI scanning. When participants realized their mind had wandered, they pressed a button and returned their focus to the breath. The four intervals above were then constructed around these button presses. We hypothesized that periods of mind wandering would be associated with default mode activity, whereas cognitive processes engaged during awareness of mind wandering, shifting of attention and sustained attention would engage attentional subnetworks. Analyses revealed activity in brain regions associated with the default mode during mind wandering, and in salience network regions during awareness of mind wandering. Elements of the executive network were active during shifting and sustained attention. Furthermore, activations during these cognitive phases were modulated by lifetime meditation experience. These findings support and extend theories about cognitive correlates of distributed brain networks.
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The impact of using motion estimates as covariates of no interest was examined in general linear modeling (GLM) of both block design and rapid event-related functional magnetic resonance imaging (fMRI) data. The purpose of motion correction is to identify and eliminate artifacts caused by task-correlated motion while maximizing sensitivity to true activations. To optimize this process, a combination of motion correction approaches was applied to data from 33 subjects performing both a block-design and an event-related fMRI experiment, including analysis: (1) without motion correction; (2) with motion correction alone; (3) with motion-corrected data and motion covariates included in the GLM; and (4) with non-motion-corrected data and motion covariates included in the GLM. Inclusion of covariates was found to be generally useful for increasing the sensitivity of GLM results in the analysis of event-related data. When motion parameters were included in the GLM for event-related data, it made little difference if motion correction was actually applied to the data. For the block design, inclusion of motion covariates had a deleterious impact on GLM sensitivity when even moderate correlation existed between motion and the experimental design. Based on these results, we present a general strategy for block designs, event-related designs, and hybrid designs to identify and eliminate probable motion artifacts while maximizing sensitivity to true activations.
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OBJECTIVE: Positron emission tomography was used to investigate the neural substrates of normal human emotional and their dependence on the types of emotional stimulus.
METHOD: Twelve healthy female subjects underwent 12 measurements of regional brain activity following the intravenous bolus administration of [15O]H2O as they alternated between emotion-generating and control film and recall tasks. Automated image analysis techniques were used to characterize and compare the increases in regional brain activity associated with the emotional response to complex visual (film) and cognitive (recall) stimuli.
RESULTS: Film- and recall-generated emotion were each associated with significantly increased activity in the vicinity of the medial prefrontal cortex and thalamus, suggesting that these regions participate in aspects of emotion that do not depend on the nature of the emotional stimulus. Film-generated emotion was associated with significantly greater increases in activity bilaterally in the occipitotemporparietal cortex, lateral cerebellum, hypothalamus, and a region that includes the anterior temporal cortex, amygdala, and hippocampal formation, suggesting that these regions participate in the emotional response to certain exteroceptive sensory stimuli. Recall-generated sadness was associated with significantly greater increases in activity in the vicinity of the anterior insular cortex, suggesting that this region participates in the emotional response to potentially distressing cognitive or interoceptive sensory stimuli.
CONCLUSIONS: While this study should be considered preliminary, it identified brain regions that participate in externally and internally generated human emotion.
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OBJECTIVE: Happiness, sadness, and disgust are three emotions that differ in their valence (positive or negative) and associated action tendencies (approach or withdrawal). This study was designed to investigate the neuroanatomical correlates of these discrete emotions.
METHOD: Twelve healthy female subjects were studied. Positron emission tomography and [15O]H2O were used to measure regional brain activity. There were 12 conditions per subject: happiness, sadness, and disgust and three control conditions, each induced by film and recall. Emotion and control tasks were alternated throughout. Condition order was pseudo-randomized and counterbalanced across subjects. Analyses focused on brain activity patterns for each emotion when combining film and recall data.
RESULTS: Happiness, sadness, and disgust were each associated with increases in activity in the thalamus and medial prefrontal cortex (Brodmann's area 9). These three emotions were also associated with activation of anterior and posterior temporal structures, primarily when induced by film. Recalled sadness was associated with increased activation in the anterior insula. Happiness was distinguished from sadness by greater activity in the vicinity of ventral mesial frontal cortex.
CONCLUSIONS: While this study should be considered preliminary, it identifies regions of the brain that participate in happiness, sadness, and disgust, regions that distinguish between positive and negative emotions, and regions that depend on both the elicitor and valence of emotion or their interaction.
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Substantial evidence suggests that a key distinction in the classification of human emotion is that between an appetitive motivational system association with positive or pleasant emotion and an aversive motivational system associated with negative or unpleasant emotion. To explore the neural substrates of these two systems, 12 healthy women viewed sets of pictures previously demonstrated to elicit pleasant, unpleasant and neutral emotion, while positron emission tomographic (PET) measurements of regional cerebral blood flow were obtained. Pleasant and unpleasant emotions were each distinguished from neutral emotion conditions by significantly increased cerebral blood flow in the vicinity of the medial prefrontal cortex (Brodmann's area 9), thalamus, hypothalamus and midbrain (P < 0.005). Unpleasant was distinguished from neutral or pleasant emotion by activation of the bilateral occipito-temporal cortex and cerebellum, and left parahippocampal gyrus, hippocampus and amygdala (P < 0.005). Pleasant was also distinguished from neutral but not unpleasant emotion by activation of the head of the left caudate nucleus (P < 0.005). These findings are consistent with those from other recent PET studies of human emotion and demonstrate that there are both common and unique components of the neural networks mediating pleasant and unpleasant emotion in healthy women.
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In children, behavioral inhibition (BI) in response to potential threat predicts the development of anxiety and affective disorders, and primate lesion studies suggest involvement of the orbitofrontal cortex (OFC) in mediating BI. Lesion studies are essential for establishing causality in brain-behavior relationships, but should be interpreted cautiously because the impact of a discrete lesion on a complex neural circuit extends beyond the lesion location. Complementary functional imaging methods assessing how lesions influence other parts of the circuit can aid in precisely understanding how lesions affect behavior. Using this combination of approaches in monkeys, we found that OFC lesions concomitantly alter BI and metabolism in the bed nucleus of stria terminalis (BNST) region and that individual differences in BNST activity predict BI. Thus it appears that an important function of the OFC in response to threat is to modulate the BNST, which may more directly influence the expression of BI.
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Positive affect elicited in a mother toward her newborn infant may be one of the most powerful and evolutionarily preserved forms of positive affect in the emotional landscape of human behavior. This study examined the neurobiology of this form of positive emotion and in so doing, sought to overcome the difficulty of eliciting robust positive affect in response to visual stimuli in the physiological laboratory. Six primiparous human mothers with no indications of postpartum depression brought their infants into the laboratory for a photo shoot. Approximately 6 weeks later, they viewed photographs of their infant, another infant, and adult faces during acquisition of functional magnetic resonance images (fMRI). Mothers exhibited bilateral activation of the orbitofrontal cortex (OFC) while viewing pictures of their own versus unfamiliar infants. While in the scanner, mothers rated their mood more positively for pictures of their own infants than for unfamiliar infants, adults, or at baseline. The orbitofrontal activation correlated positively with pleasant mood ratings. In contrast, areas of visual cortex that also discriminated between own and unfamiliar infants were unrelated to mood ratings. These data implicate the orbitofrontal cortex in a mother's affective responses to her infant, a form of positive emotion that has received scant attention in prior human neurobiological studies. Furthermore, individual variations in orbitofrontal activation to infant stimuli may reflect an important dimension of maternal attachment.
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Neuroimage phenotyping for psychiatric and neurological disorders is performed using voxelwise analyses also known as voxel based analyses or morphometry (VBM). A typical voxelwise analysis treats measurements at each voxel (e.g., fractional anisotropy, gray matter probability) as outcome measures to study the effects of possible explanatory variables (e.g., age, group) in a linear regression setting. Furthermore, each voxel is treated independently until the stage of correction for multiple comparisons. Recently, multi-voxel pattern analyses (MVPA), such as classification, have arisen as an alternative to VBM. The main advantage of MVPA over VBM is that the former employ multivariate methods which can account for interactions among voxels in identifying significant patterns. They also provide ways for computer-aided diagnosis and prognosis at individual subject level. However, compared to VBM, the results of MVPA are often more difficult to interpret and prone to arbitrary conclusions. In this paper, first we use penalized likelihood modeling to provide a unified framework for understanding both VBM and MVPA. We then utilize statistical learning theory to provide practical methods for interpreting the results of MVPA beyond commonly used performance metrics, such as leave-one-out-cross validation accuracy and area under the receiver operating characteristic (ROC) curve. Additionally, we demonstrate that there are challenges in MVPA when trying to obtain image phenotyping information in the form of statistical parametric maps (SPMs), which are commonly obtained from VBM, and provide a bootstrap strategy as a potential solution for generating SPMs using MVPA. This technique also allows us to maximize the use of available training data. We illustrate the empirical performance of the proposed framework using two different neuroimaging studies that pose different levels of challenge for classification using MVPA.
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Our outside world changes continuously, for example, when driving through traffic. An important question is how our brain deals with this constant barrage of rapidly changing sensory input and flexibly selects only newly goal-relevant information for further capacity-limited processing in working memory. The challenge our brain faces is experimentally captured by the attentional blink (AB): an impairment in detecting the second of two target stimuli presented in close temporal proximity among distracters. Many theories have been proposed to explain this deficit in processing goal-relevant information, with some attributing the AB to capacity limitations related to encoding of the first target and others assigning a critical role to on-line selection mechanisms that control access to working memory. The current study examined the role of striatal dopamine in the AB, given its known role in regulating the contents of working memory. Specifically, participants performed an AB task and their basal level of dopamine D2-like receptor binding was measured using PET and [F-18]fallypride. As predicted, individual differences analyses showed that greater D2-like receptor binding in the striatum was associated with a larger AB, implicating striatal dopamine and mechanisms that control access to working memory in the AB. Specifically, we propose that striatal dopamine may determine the AB by regulating the threshold for working memory updating, providing a testable physiological basis for this deficit in gating rapidly changing visual information. A challenge for current models of the AB lies in connecting more directly to these neurobiological data.
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Increasing research indicates that concepts are represented as distributed circuits of property information across the brain's modality-specific areas. The current study examines the distributed representation of an important but under-explored category, foods. Participants viewed pictures of appetizing foods (along with pictures of locations for comparison) during event-related fMRI. Compared to location pictures, food pictures activated the right insula/operculum and the left orbitofrontal cortex, both gustatory processing areas. Food pictures also activated regions of visual cortex that represent object shape. Together these areas contribute to a distributed neural circuit that represents food knowledge. Not only does this circuit become active during the tasting of actual foods, it also becomes active while viewing food pictures. Via the process of pattern completion, food pictures activate gustatory regions of the circuit to produce conceptual inferences about taste. Consistent with theories that ground knowledge in the modalities, these inferences arise as reenactments of modality-specific processing.
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Individuals with fragile X syndrome (FXS) commonly display characteristics of social anxiety, including gaze aversion, increased time to initiate social interaction, and difficulty forming meaningful peer relationships. While neural correlates of face processing, an important component of social interaction, are altered in FXS, studies have not examined whether social anxiety in this population is related to higher cognitive processes, such as memory. This study aimed to determine whether the neural circuitry involved in face encoding was disrupted in individuals with FXS, and whether brain activity during face encoding was related to levels of social anxiety. A group of 11 individuals with FXS (5 M) and 11 age- and gender-matched control participants underwent fMRI scanning while performing a face encoding task with online eye-tracking. Results indicate that compared to the control group, individuals with FXS exhibited decreased activation of prefrontal regions associated with complex social cognition, including the medial and superior frontal cortex, during successful face encoding. Further, the FXS and control groups showed significantly different relationships between measures of social anxiety (including gaze-fixation) and brain activity during face encoding. These data indicate that social anxiety in FXS may be related to the inability to successfully recruit higher level social cognition regions during the initial phases of memory formation.
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BACKGROUND: Anhedonia, a reduced ability to experience pleasure, is a chief symptom of major depressive disorder and is related to reduced frontostriatal connectivity when attempting to upregulate positive emotion. The present study examined another facet of positive emotion regulation associated with anhedonia-namely, the downregulation of positive affect-and its relation to prefrontal cortex (PFC) activity.
METHODS: Neuroimaging data were collected from 27 individuals meeting criteria for major depressive disorder as they attempted to suppress positive emotion during a positive emotion regulation task. Their PFC activation pattern was compared with the PFC activation pattern exhibited by 19 healthy control subjects during the same task. Anhedonia scores were collected at three time points: at baseline (time 1), 8 weeks after time 1 (i.e., time 2), and 6 months after time 1 (i.e., time 3). Prefrontal cortex activity at time 1 was used to predict change in anhedonia over time. Analyses were conducted utilizing hierarchical linear modeling software.
RESULTS: Depressed individuals who could not inhibit positive emotion-evinced by reduced right ventrolateral prefrontal cortex activity during attempts to dampen their experience of positive emotion in response to positive visual stimuli-exhibited a steeper anhedonia reduction slope between baseline and 8 weeks of treatment with antidepressant medication (p < .05). Control subjects showed a similar trend between baseline and time 3.
CONCLUSIONS: To reduce anhedonia, it may be necessary to teach individuals how to counteract the functioning of an overactive pleasure-dampening prefrontal inhibitory system.
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Significant progress has been made in our understanding of the neural substrates of emotion and its disorders. Neuroimaging methods have been used to characterize the circuitry underlying disorders of emotion. Particular emphasis has been placed on the prefrontal cortex, anterior cingulate, parietal cortex, and the amygdala as critical components of the circuitry that may be dysfunctional in both depression and anxiety.
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