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Articles by Gregory McCarthy in JoVE

 JoVE Neuroscience

Brain Imaging Undersøgelse af forringe Effekt af Emotion på kognition


JoVE 2434 2/01/2012

1Department of Psychiatry, University of Alberta, 2Centre for Neuroscience, University of Alberta, 3Department of Psychology, University of Illinois, 4Brain Imaging and Analysis Center, Duke University, 5Department of Psychiatry and Behavioral Sciences, Duke University, 6Mid-Atlantic Mental Illness Research Education and Clinical Center, VA Medical Center, 7Department of Psychology, Yale University, 8Neuroscience Program, University of Illinois, 9Beckman Institute for Advanced Science & Technology, University of Illinois

Vi præsenterer en protokol, der giver mulighed for undersøgelse af de neurale mekanismer, medierende de skadelige virkninger af følelser på kognition, ved hjælp af funktionel magnetisk resonans billeddannelse. Denne protokol kan bruges med både sund og kliniske deltagere.

Other articles by Gregory McCarthy on PubMed

Electrophysiological Studies of Face Perception in Humans

Event-related potentials (ERPs) associated with face perception were recorded with scalp electrodes from normal volunteers. Subjects performed a visual target detection task in which they mentally counted the number of occurrences of pictorial stimuli from a designated category such us butterflies. In separate experiments, target stimuli were embedded within a series of other stimuli including unfamiliar human faces and isolated face components, inverted faces, distorted faces, animal faces, and other nonface stimuli. Unman faces evoked a negative potential at 172 msec (N170), which was absent from the ERPs elicited by other animate and inanimate nonface stimuli. N170 was largest over the posterior temporal scalp and was larger over the right than the left hemisphere. N170 was delayed when faces were presented upside-down, but its amplitude did not change. When presented in isolation, eyes elicited an N170 that was significantly larger than that elicited by whole faces, while noses and lips elicited small negative ERPs about 50 msec later than N170. Distorted human faces, in which the locations of inner face components were altered, elicited an N170 similar in amplitude to that elicited by normal faces. However, faces of animals, human hands, cars, and items of furniture did not evoke N170. N170 may reflect the operation of a neural mechanism tuned to detect (as opposed to identify) human faces, similar to the "structural encoder" suggested by Bruce and Young (1986). A similar function has been proposed for the face-selective N200 ERP recorded from the middle fusiform and posterior inferior temporal gyri using subdural electrodes in humans (Allison, McCarthy, Nobre, Puce, & Belger, 1994c). However, the differential sensitivity of N170 to eyes in isolation suggests that N170 may reflect the activation of an eye-sensitive region of cortex. The voltage distribution of N170 over the scalp is consistent with a neural generator located in the occipitotemporal sulcus lateral to the fusiform/inferior temporal region that generates N200.

Tris(benzylthiolato)bismuth. Efficient Precursor to Phase-Pure Polycrystalline Bi(2)S(3)

Details of the synthesis, physical and spectroscopic characterization, and thermal decomposition of tris(benzylthiolato)bismuth, (BnS)(3)Bi, Bn = CH(2)C(6)H(5), are presented. Results from pyrolysis of (BnS)(3)Bi demonstrate that this compound is a convenient precursor to phase-pure, polycrystalline Bi(2)S(3) with low carbon and hydrogen contamination under mild thermal conditions (ca. 275 degrees C). Flow-tube pyrolysis produces small ( approximately 1 &mgr;m) spherical particles, whereas sealed-tube pyrolysis produces 6-&mgr;m diameter spherical particles composed of radiating acicular crystallites. Bi(2)S(3) was characterized by X-ray powder diffraction and scanning electron microscopy.

Perceiving Patterns in Random Series: Dynamic Processing of Sequence in Prefrontal Cortex

We demonstrate that regions within human prefrontal cortex develop moment-to-moment models for patterns of events occurring in the sensory environment. Subjects viewed a random binary sequence of images, each presented singly and each requiring a different button press response. Patterns occurred by chance within the presented series of images. Using functional magnetic resonance imaging (fMRI), we identified activity evoked by viewing a stimulus that interrupted a pattern. Prefrontal activation was evoked by violations of both repeating and alternating patterns, and the amplitude of this activation increased with increasing pattern length. Violations of repeating patterns, but not of alternating patterns, activated the basal ganglia.

Field Potentials in the Human Hippocampus During the Encoding and Recognition of Visual Stimuli

Intracranial field potentials were recorded from electrodes implanted in the hippocampus in 12 epileptic patients. Potentials were elicited by stimuli presented during a delayed matching-to-sample test. Each trial began with a sample stimulus composed of a 3 x 3 grid of rectangular color patches. The sample was followed by a sequence of similar but task-irrelevant stimuli and the sequential presentation of two test stimuli, one of which was identical to the sample. Patients indicated their recognition of the test stimulus that matched the sample with a button press. High-amplitude negative potentials were consistently elicited by sample and test stimuli. Peak amplitudes occurred 300-500 ms after stimulus onset and were larger for the sample in all cases. The patterns of potential gradients observed between adjacent hippocampal contacts and the locations of maximal amplitudes, as verified by magnetic resonance imaging in seven patients, suggest that these potentials were produced by neuronal activity in posterior hippocampus. These field potentials appear to index a memory storage function engaged in response to events that will later be remembered. The hippocampal contribution to storing declarative memories can thus begin, in some circumstances, within the first half-second after the presentation of a to-be-remembered stimulus.

Dissociable Prefrontal Brain Systems for Attention and Emotion

The prefrontal cortex has been implicated in a variety of attentional, executive, and mnemonic mental operations, yet its functional organization is still highly debated. The present study used functional MRI to determine whether attentional and emotional functions are segregated into dissociable prefrontal networks in the human brain. Subjects discriminated infrequent and irregularly presented attentional targets (circles) from frequent standards (squares) while novel distracting scenes, parametrically varied for emotional arousal, were intermittently presented. Targets differentially activated middle frontal gyrus, posterior parietal cortex, and posterior cingulate gyrus. Novel distracters activated inferior frontal gyrus, amygdala, and fusiform gyrus, with significantly stronger activation evoked by the emotional scenes. The anterior cingulate gyrus was the only brain region with equivalent responses to attentional and emotional stimuli. These results show that attentional and emotional functions are segregated into parallel dorsal and ventral streams that extend into prefrontal cortex and are integrated in the anterior cingulate. These findings may have implications for understanding the neural dynamics underlying emotional distractibility on attentional tasks in affective disorders.

Deterministic and Stochastic Features of FMRI Data: Implications for Analysis of Event-related Experiments

As the limits of stimuli presentation rates are explored in event-related fMRI design, there is a greater need to assess the implications of averaging raw fMRI data. Selective averaging assumes that the fMRI signal consists of task-dependent signal, random noise, and non-task dependent brain signal that can be modeled as random noise so that it tends to zero when averaged over a practical number of trials. We recorded a total of four fMRI data series from two normal subjects (subject 1, axially acquired; subject 2, coronally acquired) performing a simple visual event-related task and a water phantom with the same fMRI scanner imaging parameters. To determine which fraction of the fMRI data was deterministic as opposed to random, we created different data subsets by taking the odd or even time points of the full data sets. All data sets were first dimension-reduced with principal component analysis (PCA) and separated into 100 spatially independent components with independent component analysis (ICA). The mutual information between best-matching pairs of components selected from full data set-subset comparisons was plotted for each data set. Visual inspection suggested that 45-85 components were reproducible, and hence deterministic, accounting for 79-97% of the variance, respectively, in the raw data. The reproducible components exhibited much less trial-to-trial variability than the raw data from even the most activated voxel. Many (22-47) of reproducible components were significantly affected by stimulus presentation (P < 0.001). The most significantly-stimulus-correlated component was strongly time-locked to stimulus presentation and was directly stimulus correlated, corresponding to occipital brain regions. However, other spatially distinct task-related components demonstrated variable temporal relationships with the most significantly-stimulus-correlated component. Our results suggest that the majority of the variance in fMRI data is in fact deterministic, and support the notion that the data consist of differing components with differing temporal relationships to visual stimulation. They further suggest roles for restricting interpretations of the spatial extent of activation from event-related designs to a specific region of interest (ROI) and/or first separating the data into spatially independent components. Averaging the time courses of spatially independent components time-locked to stimulus presentation may prevent possible biases in the estimates of the spatial and temporal extent of stimulus-correlated activation and of trial-to-trial variability.

Enhanced Spatial Localization of Neuronal Activation Using Simultaneous Apparent-diffusion-coefficient and Blood-oxygenation Functional Magnetic Resonance Imaging

Functional MRI (fMRI) can detect blood oxygenation level dependent (BOLD) hemodynamic responses secondary to local neuronal activity. The most commonly used method for detecting fMRI signals is the gradient-echo echo-planar imaging (EPI) technique because of its sensitivity and speed. However, it is known that much of the signal obtained with this approach arises from large veins, with additional contribution from the capillaries and venules. Early experiments using diffusion-weighted gradient-echo EPI have suggested that intravoxel incoherent motion (IVIM) weighting can selectively attenuate contributions from large vessels based on the differences in the mobility of the blood within them, thereby revealing the contributions from hemodynamic changes in capillaries, which are in close spatial proximity to the activated neural tissue. Using this differential sensitivity of the various neurovascular compartments to IVIM weighting, we present a new approach for deriving functional maps of neural activity. This method is based on task-induced changes of the apparent diffusion coefficients (ADC), a signal that we demonstrate is generated in vascular compartments that only partially overlap with those generating the BOLD signal. The approach allows both the ADC-based maps and the more commonly used BOLD-based maps to be acquired simultaneously. The spatial overlap between these maps can be used to create composite maps that permit improved localization of the underlying neuronal activity patterns by identifying signals generated in those vascular components that are in closest proximity to the active neuronal populations of interest.

Category-sensitive Excitatory and Inhibitory Processes in Human Extrastriate Cortex

Single-cell recordings from the temporal lobe of monkeys viewing stimuli show that cells may be highly selective, responding for example to particular objects such as faces. However, stimulus-selective cells may be inhibited by nonpreferred stimuli. Can such inhibitory mechanisms be detected in human visual cortex? In previous recordings from the surface of human ventral extrastriate cortex, we found that specific categories of stimuli such as faces and words generate category-specific negative event-related potentials (ERPs) with a peak latency of about 200 ms (N200). Laminar recordings in animal cortex suggest that the human N200 reflects excitatory depolarizing potentials in apical dendrites of pyramidal cells. In this study we found that, at about half of word-specific N200 sites, faces generated a positive ERP (P200); conversely, at about half of face-specific sites, words generated P200s. The electrogenesis of N200 implies that P200 ERPs reflect hyperpolarizing inhibition of apical dendrites. These recordings, together with the prior animal recordings, provide strong circumstantial evidence that in human cortex populations of cells responsive to one stimulus category (such as faces) inhibit cells responsive to another category (such as words), probably by a type of lateral inhibition. Of the stimulus categories studied quantitatively, face-specific cells are maximally inhibited by words and vice versa, but other categories of stimuli may generate smaller P200s, suggesting that inhibition of category-specific cells by nonpreferred stimuli is a general feature of human extrastriate cortex involved in object recognition.

Brain Activation Evoked by Perception of Gaze Shifts: the Influence of Context

Prior studies from our laboratory [Journal of Neuroscience 18 (1998) 2188; Cognitive Neuropsychology 17 (2000) 221] have demonstrated that discrete regions of the superior temporal sulcus (STS) are activated when a subject views a face in which the eyes shift their gaze. Here we investigated the degree to which activity in the STS and other brain regions is modulated by the context of the perceived gaze shift; that is, when the shift correctly or incorrectly acquires a visual target. Fifteen subjects participated in an event-related functional magnetic resonance imaging experiment in which they viewed an animated face that remained present throughout each run. On each of 21 trials within each run, a small checkerboard appeared and flickered at one of six locations within the character's visual field. On "correct" trials, the character shifted its gaze towards the checkerboard after a delay of 1 or 3s. On "incorrect" trials, the character shifted its gaze towards empty space after the same delays. On "no shift" trials, the character's eyes did not move. Significantly larger hemodynamic responses (HDR) were evoked by gaze shifts compared to no gaze shifts in primarily right hemisphere STS. The gaze-evoked HDR was significantly delayed in peak amplitude for 3s compared to 1s shifts. For 1s shifts, a strong effect of context was observed in which errors evoked a HDR with extended duration. Although this study focused upon STS, similar effects were also observed in the intraparietal sulcus and fusiform gyrus.

Faces Evoke Spatially Differentiated Patterns of BOLD Activation and Deactivation

Using fMRI techniques sensitive to blood oxygen-level dependent (BOLD) contrast, we measured brain activity in participants (n=8) as they viewed images of faces presented periodically within a continuously changing montage of common objects. Consistent with prior studies, we identified regions of ventral extrastriate cortex, primarily in the fusiform and inferior temporal gyri and nearby cortex, that were activated by faces as measured by an increase in BOLD signal. In addition, we made the novel observation that faces deactivated other areas of ventral extrastriate cortex, primarily in the lingual and parahippocampal gyri and medial to activations. These deactivated regions, identified by a decrease in BOLD signal, may reflect populations of neurons that decrease their activity when faces appear, possibly as a consequence of category-specific inhibition.

Brain Activity Evoked by the Perception of Human Walking: Controlling for Meaningful Coherent Motion

Many functional neuroimaging studies of biological motion have used as stimuli point-light displays of walking figures and compared the resulting activations with those evoked by the same display elements moving in a random or noncoherent manner. Although these studies have established that biological motion activates the superior temporal sulcus (STS), the use of random motion controls has left open the possibility that coordinated and meaningful nonbiological motion might activate these same brain regions and thus call into question their specificity for processing biological motion. Here we used functional magnetic resonance imaging and an anatomical region-of-interest approach to test a hierarchy of three questions regarding activity within the STS. First, by comparing responses in the STS with animations of human and robot walking figures, we determined (1) that the STS is sensitive to biological motion itself, not merely to the superficial characteristics of the stimulus. Then we determined that the STS responds more strongly to biological motion (as conveyed by the walking robot) than to (2) a nonmeaningful but complex nonbiological motion (a disjointed mechanical figure) and (3) a complex and meaningful nonbiological motion (the movements of a grandfather clock). In subsequent whole-brain voxel-based analyses, we confirmed robust STS activity that was strongly right lateralized. In addition, we observed significant deactivations in the STS that differentiated biological and nonbiological motion. These voxel-based analyses also revealed regions of motion-related positive activity in other brain regions, including MT or V5, fusiform gyri, right premotor cortex, and the intraparietal sulci.

Dynamic Perception of Facial Affect and Identity in the Human Brain

Functional magnetic resonance imaging (fMRI) was used to compare brain activation to static facial displays versus dynamic changes in facial identity or emotional expression. Static images depicted prototypical fearful, angry and neutral expressions. Identity morphs depicted identity changes from one person to another, always with neutral expressions. Emotion morphs depicted expression changes from neutral to fear or anger, creating the illusion that the actor was 'getting scared' or 'getting angry' in real-time. Brain regions implicated in processing facial affect, including the amygdala and fusiform gyrus, showed greater responses to dynamic versus static emotional expressions, especially for fear. Identity morphs activated a dorsal fronto-cingulo-parietal circuit and additional ventral areas, including the amygdala, that also responded to the emotion morphs. Activity in the superior temporal sulcus discriminated emotion morphs from identity morphs, extending its known role in processing biologically relevant motion. The results highlight the importance of temporal cues in the neural coding of facial displays.

Polysensory Interactions Along Lateral Temporal Regions Evoked by Audiovisual Speech

Many socially significant biological stimuli are polymodal, and information processing is enhanced for polymodal over unimodal stimuli. The human superior temporal sulcus (STS) region has been implicated in processing socially relevant stimuli--particularly those derived from biological motion such as mouth movements. Single unit studies in monkeys have demonstrated that regions of STS are polysensory--responding to visual, auditory and somato-sensory stimuli, and human neuroimaging studies have shown that lip-reading activates auditory regions of the lateral temporal lobe. We evaluated whether concurrent speech sounds and mouth movements were more potent activators of STS than either speech sounds or mouth movements alone. In an event-related fMRI study, subjects observed an animated character that produced audiovisual speech and the audio and visual components of speech alone. Strong activation of the STS region was evoked in all three conditions, with greatest levels of activity elicited by audiovisual speech. Subsets of activated voxels within the STS region demonstrated overadditivity (audiovisual > audio + visual) and underadditivity (audiovisual < audio + visual). These results confirm the polysensory nature of STS region and demonstrate for the first time that polymodal interactions may both potentiate and inhibit activation.

What is Odd in the Oddball Task? Prefrontal Cortex is Activated by Dynamic Changes in Response Strategy

In the "oddball" target detection task, subjects respond to target stimuli that occur infrequently and irregularly within a series of standard stimuli. Although detection of these targets reliably evokes transient activity in prefrontal cortical regions, it has not been established whether this activity is due to selection of an infrequent response or to changes in response strategy. We investigated this issue using a novel variant of the oddball task that incorporated the Simon effect, while measuring hemodynamic brain activity in prefrontal cortex using functional magnetic resonance imaging (fMRI). Subjects viewed a series of circles and squares that required left and right button presses, respectively. On 90% of trials ("standard" trials), the stimuli were presented in the same visual hemifield as the hand of response, but on 10% of trials ("strategy-change" trials) they were presented in the opposite visual hemifield. Significant activation to the infrequent strategy-change trials was found in the anterior middle frontal gyrus (MFG), the posterior inferior frontal gyrus (IFG) and adjacent insular cortex, and in the anterior cingulate gyrus (ACG). These regions, which correspond to previous reports of oddball-related activation, were consistent across subjects. Behavioral results supported our interpretation that subjects potentiated a position-based response strategy, which was inhibited on the strategy-change trials. Activity within the MFG and ACG was much greater on error trials than on correct trials, while IFG activity was similar between error and correct trials. We conclude that the dorsolateral prefrontal cortex (dlPFC) is associated with dynamic changes in the mapping of stimuli to responses (e.g. response strategies), independently of any changes in behavior.

Linking Hemodynamic and Electrophysiological Measures of Brain Activity: Evidence from Functional MRI and Intracranial Field Potentials

We investigated the relation between electrophysiological and hemodynamic measures of brain activity through comparison of intracranially recorded event-related local field potentials (ERPs) and blood-oxygenation level dependent functional magnetic resonance imaging (BOLD fMRI). We manipulated the duration of visual checkerboard stimuli across trials and measured stimulus-duration-related changes in ERP and BOLD activity in three brain regions: peri-calcarine cortex, the fusiform gyrus and lateral temporal-occipital (LTO) cortex. ERPs were recorded from patients who had indwelling subdural electrodes as part of presurgical testing, while BOLD responses were measured in similar brain regions in a second set of subjects. Similar BOLD responses were measured in peri-calcarine and fusiform regions, with both showing monotonic but non-linear increases in hemodynamic amplitude with stimulus duration. In sharp contrast, very different ERP responses were observed in these same regions, such that calcarine electrodes exhibited onset potentials, sustained activity over the course of stimulus duration and prominent offset potentials, while fusiform electrodes only exhibited onset potentials that did not vary with stimulus duration. No duration-related ERP or BOLD changes were observed in LTO. Additional analyses revealed no consistent changes in the EEG spectrum across different brain sites that correlated with duration-related changes in the BOLD response. We conclude that the relation between ERPs and fMRI differs across brain regions.

Dynamic and Strategic Aspects of Executive Processing

Executive cognitive functions have been postulated to include both dynamic behavioral selection and strategic goal-setting or response preparation. To investigate the relation between these aspects of executive processing, we embedded an event-related oddball paradigm within a blocked design. Subjects responded to infrequent targets presented within a series of standard stimuli that required no response; this task alternated with a visually similar nontask condition. Using functional magnetic resonance imaging (fMRI), we found that a set of brain regions including dorsolateral prefrontal cortex (dlPFC), insular cortex, cingular cortex, and the basal ganglia demonstrated transient activation both to target stimuli and to the onset of task blocks. Within the parietal cortex, there was a dissociation such that the supramarginal gyrus exhibited greater activity to the target stimuli than to block onsets, while the converse pattern was observed in the intraparietal sulcus. Sustained positive activity during task blocks was present in the caudate and supplementary motor area, while sustained negative activity was present in the precuneus and medial parietal cortex. We conclude that dlPFC and related brain regions mediate both dynamic and strategic processing, through the preparation and selection of rules for behavior.

Emotion-attention Network Interactions During a Visual Oddball Task

Emotional and attentional functions are known to be distributed along ventral and dorsal networks in the brain, respectively. However, the interactions between these systems remain to be specified. The present study used event-related functional magnetic resonance imaging (fMRI) to investigate how attentional focus can modulate the neural activity elicited by scenes that vary in emotional content. In a visual oddball task, aversive and neutral scenes were presented intermittently among circles and squares. The squares were frequent standard events, whereas the other novel stimulus categories occurred rarely. One experimental group [N=10] was instructed to count the circles, whereas another group [N=12] counted the emotional scenes. A main effect of emotion was found in the amygdala (AMG) and ventral frontotemporal cortices. In these regions, activation was significantly greater for emotional than neutral stimuli but was invariant to attentional focus. A main effect of attentional focus was found in dorsal frontoparietal cortices, whose activity signaled task-relevant target events irrespective of emotional content. The only brain region that was sensitive to both emotion and attentional focus was the anterior cingulate gyrus (ACG). When circles were task-relevant, the ACG responded equally to circle targets and distracting emotional scenes. The ACG response to emotional scenes increased when they were task-relevant, and the response to circles concomitantly decreased. These findings support and extend prominent network theories of emotion-attention interactions that highlight the integrative role played by the anterior cingulate.

When Strangers Pass: Processing of Mutual and Averted Social Gaze in the Superior Temporal Sulcus

Using functional magnetic resonance imaging (fMRI), we investigated brain activity evoked by mutual and averted gaze in a compelling and commonly experienced social encounter. Through virtual-reality goggles, subjects viewed a man who walked toward them and shifted his neutral gaze either toward (mutual gaze) or away (averted gaze) from them. Robust activity was evoked in the superior temporal sulcus (STS) and fusiform gyrus (FFG). For both conditions, STS activity was strongly right lateralized. Mutual gaze evoked greater activity in the STS than did averted gaze, whereas the FFG responded equivalently to mutual and averted gaze. Thus, we show that the STS is involved in processing social information conveyed by shifts in gaze within an overtly social context. This study extends understanding of the role of the STS in social cognition and social perception by demonstrating that it is highly sensitive to the context in which a human action occurs.

Grasping the Intentions of Others: the Perceived Intentionality of an Action Influences Activity in the Superior Temporal Sulcus During Social Perception

An explication of the neural substrates for social perception is an important component in the emerging field of social cognitive neuroscience and is relevant to the field of cognitive neuroscience as a whole. Prior studies from our laboratory have demonstrated that passive viewing of biological motion (Pelphrey, Mitchell, et al., 2003; Puce et al., 1998) activates the posterior superior temporal sulcus (STS ) region. Furthermore, recent evidence has shown that the perceived context of observed gaze shifts (Pelphrey, Singerman, et al., 2003; Pelphrey et al., 2004) modulates STS activity. Here, using event-related functional magnetic resonance imaging at 4 T, we investigated brain activity in response to passive viewing of goal- and nongoal-directed reaching-to-grasp movements. Participants viewed an animated character making reaching-to-grasp movements either toward (correct) or away (incorrect) from a blinking dial. Both conditions evoked significant posterior STS activity that was strongly right lateralized. By examining the time course of the blood oxygenation level-dependent response from areas of activation, we observed a functional dissociation. Incorrect trials evoked significantly greater activity in the STS than did correct trials, while an area posterior and inferior to the STS (likely corresponding to the MT/ V5 complex) responded equally to correct and incorrect movements. Parietal cortical regions, including the superior parietal lobule and the anterior intraparietal sulcus, also responded equally to correct and incorrect movements, but showed evidence for differential responding based on the hand and arm (left or right) of the animated character used to make the reaching-to-grasp movement. The results of this study further suggest that a region of the right posterior STS is involved in analyzing the intentions of other people's actions and that activity in this region is sensitive to the context of observed biological motions.

FMRI Signal Source Analysis Using Diffusion-weighted Spiral-in Acquisition

Despite the tremendous growth in functional magnetic resonance imaging (fMRI), susceptibility induced static field inhomogeneity at air/tissue interface have limited the study of ventral brain regions engaged in object recognition and other processes. Furthermore, the spatial extent of fMRI activations in this region may be obscured by contribution of large vessels distant from the precipitating neural events. In this report, a diffusion weighted spiral-in image acquisition was employed to recover fMRI signal in the ventral brain during object recognition with high temporal resolution, as well as to suppress large vessel contributions. The combined methodology of the ventral signal recovery and vascular signal reduction can thus be advantageous for fMRI investigations at the statically inhomogeneous areas.

Functional Anatomy of Biological Motion Perception in Posterior Temporal Cortex: an FMRI Study of Eye, Mouth and Hand Movements

Passive viewing of biological motion engages extensive regions of the posterior temporal-occipital cortex in humans, particularly within and nearby the superior temporal sulcus (STS). Relatively little is known about the functional specificity of this area. Some recent studies have emphasized the perceived intentionality of the motion as a potential organizing principle, while others have suggested the existence of a somatotopy based upon the limb perceived in motion. Here we conducted an event-related functional magnetic resonance imaging experiment to compare activity elicited by movement of the eyes, mouth or hand. Each motion evoked robust activation in the right posterior temporal-occipital cortex. While there was substantial overlap of the activation maps in this region, the spatial distribution of hemodynamic response amplitudes differentiated the movements. Mouth movements elicited activity along the mid-posterior STS while eye movements elicited activity in more superior and posterior portions of the right posterior STS region. Hand movements activated more inferior and posterior portions of the STS region within the posterior continuing branch of the STS. Hand-evoked activity also extended into the inferior temporal, middle occipital and lingual gyri. This topography may, in part, reflect the role of particular body motions in different functional activities.

Amygdala Activation to Sad Pictures During High-field (4 Tesla) Functional Magnetic Resonance Imaging

Fear-related processing in the amygdala has been well documented, but its role in signaling other emotions remains controversial. The authors recovered signal loss in the amygdala at high-field strength using an inward spiral pulse sequence and probed its response to pictures varying in their degree of portrayed sadness. These pictures were presented as intermittent task-irrelevant distractors during a concurrent visual oddball task. Relative to neutral distractors, sad distractors elicited greater activation along ventral brain regions, including the amygdala, fusiform gyrus, and inferior frontal gyrus. In contrast, oddball targets engaged dorsal sectors of frontal, parietal, and cingulate cortices. The amygdala's role in emotional evaluation thus extends to images of grief and despair as well as to those depicting violence and threat.

Neural Basis of Eye Gaze Processing Deficits in Autism

Impairments in using eye gaze to establish joint attention and to comprehend the mental states and intentions of other people are striking features of autism. Here, using event-related functional MRI (fMRI), we show that in autism, brain regions involved in gaze processing, including the superior temporal sulcus (STS) region, are not sensitive to intentions conveyed by observed gaze shifts. On congruent trials, subjects watched as a virtual actor looked towards a checkerboard that appeared in her visual field, confirming the subject's expectation regarding what the actor 'ought to do' in this context. On incongruent trials, she looked towards empty space, violating the subject's expectation. Consistent with a prior report from our laboratory that used this task in neurologically normal subjects, 'errors' (incongruent trials) evoked more activity in the STS and other brain regions linked to social cognition, indicating a strong effect of intention in typically developing subjects (n = 9). The same brain regions were activated during observation of gaze shifts in subjects with autism (n = 10), but did not differentiate congruent and incongruent trials, indicating that activity in these regions was not modulated by the context of the perceived gaze shift. These results demonstrate a difference in the response of brain regions underlying eye gaze processing in autism. We conclude that lack of modulation of the STS region by gaze shifts that convey different intentions contributes to the eye gaze processing deficits associated with autism.

Decisions Under Uncertainty: Probabilistic Context Influences Activation of Prefrontal and Parietal Cortices

Many decisions are made under uncertainty; that is, with limited information about their potential consequences. Previous neuroimaging studies of decision making have implicated regions of the medial frontal lobe in processes related to the resolution of uncertainty. However, a different set of regions in dorsal prefrontal and posterior parietal cortices has been reported to be critical for selection of actions to unexpected or unpredicted stimuli within a sequence. In the current study, we induced uncertainty using a novel task that required subjects to base their decisions on a binary sequence of eight stimuli so that uncertainty changed dynamically over time (from 20 to 50%), depending on which stimuli were presented. Activation within prefrontal, parietal, and insular cortices increased with increasing uncertainty. In contrast, within medial frontal regions, as well as motor and visual cortices, activation did not increase with increasing uncertainty. We conclude that the brain response to uncertainty depends on the demands of the experimental task. When uncertainty depends on learned associations between stimuli and responses, as in previous studies, it modulates activation in the medial frontal lobes. However, when uncertainty develops over short time scales as information is accumulated toward a decision, dorsal prefrontal and posterior parietal contributions are critical for its resolution. The distinction between neural mechanisms subserving different forms of uncertainty resolution provides an important constraint for neuroeconomic models of decision making.

Visual Task Complexity Modulates the Brain's Response to Unattended Auditory Novelty

New, unusual, and changing events are important environmental cues, and the ability to detect these types of stimuli in the environment constitutes a biologically significant survival skill. We used event-related potentials to examine whether sensory and cognitive neural responses to unattended novel events are modulated by the complexity of a primary visuomotor task. Event-related potentials were elicited by unattended task-irrelevant pitch-deviant tones and novel environmental sounds while study participants performed a continuous visuomotor tracking task at two levels of difficulty, achieved by manipulating the control dynamics of a joystick. The results revealed that increased task complexity modulated evoked sensory and cognitive event-related potential components, indicating that detection of change and novelty in the unattended auditory channel is resource-limited.

Taking an "intentional Stance" on Eye-gaze Shifts: a Functional Neuroimaging Study of Social Perception in Children

During middle childhood, children develop an increasing understanding of intentions and other social information conveyed through dynamic facial cues such as changes in eye-gaze direction. Recent work in our laboratory has focused on using functional magnetic resonance imaging (fMRI) in adults to map the neural circuitry subserving the visual analysis of others' actions and the intentions underlying these actions. In these studies, the superior temporal sulcus (STS) region has been continually implicated in processing shifts in eye gaze. Further, these studies have indicated that STS activity is modulated by the context within which eye-gaze shifts occur, suggesting that this region is involved in social perception via its role in the analysis of the intentions of observed actions. Still, no studies have investigated the neural circuitry supporting eye-gaze processing in children. We used event-related fMRI to examine brain activity in 7- to 10-year-old healthy children observing an animated virtual actor who shifted her eyes towards either a target object or empty space. Consistent with prior studies in adults, the STS, middle temporal gyrus, and inferior parietal lobule were sensitive to the intentions underlying the stimulus character's eye movements. These findings suggest that the neural circuitry underlying the processing of eye gaze and the detection of intentions conveyed through shifts in eye gaze in children are similar to that found previously in adults. We discuss these findings and potential implications for mapping the neurodevelopment of the social cognition and social perception abnormalities characteristic of autism.

Regional Brain Activation Evoked when Approaching a Virtual Human on a Virtual Walk

We investigated the necessity of biological motion for activation of the posterior superior temporal sulcus (pSTS) in circumstances in which the rapid approach of the observer to a virtual human induced the observer to make inferences about the characters intentions. Using a virtual reality environment, subjects experienced themselves walking towards a complex scene composed of animate and/or inanimate objects. During "person" trials, the scene contained a virtual human either making a simple gesture such as scratching his face (Study 1) or standing completely still (Study 2). During "object" trials, the scenes contained items such as furniture, a face portrait, and a clock, but not the virtual human. Using functional MRI to measure brain activity, we demonstrated strong activity in the pSTS while the observer approached the social scene, but only when the virtual human was making gestures. This result emphasizes the importance of biological motion in inferring the intentions of others.

Graded Visual Attention Modulates Brain Responses Evoked by Task-irrelevant Auditory Pitch Changes

Previous studies suggested that auditory change-specific neural responses are attention-independent and reflect central auditory processing. The automaticity of the brain's response to infrequent changes in pitch within a series of auditory tone pips was examined in parallel functional magnetic resonance imaging (fMRI) and event-related potential (ERP) studies. Subjects performed a continuous perceptual-motor visual tracking task at two levels of difficulty while simultaneously hearing a series of task-irrelevant standard tone pips and infrequent pitch-deviant tones. fMRI results revealed that the unattended pitch-deviant tones strongly activated superior temporal and frontal cortical regions. These activations were significantly modulated by the tracking difficulty of the primary task. ERP results revealed that the amplitude of the scalp-negative component evoked by deviant tones (MMN) was attenuated during the more difficult tracking task. Our results demonstrate that the brain's response to task-irrelevant sensory changes is strongly influenced by intermodal attentional demands.

Brain Systems Mediating Cognitive Interference by Emotional Distraction

Flexible behavior depends on our ability to cope with distracting stimuli that can interfere with the attainment of goals. Emotional distracters can be particularly disruptive to goal-oriented behavior, but the neural systems through which these detrimental effects are mediated are not known. We used event-related functional magnetic resonance imaging to investigate the effect of emotional and nonemotional distracters on a delayed-response working memory (WM) task. As expected, this task evoked robust activity during the delay period in typical WM regions (dorsolateral prefrontal cortex and lateral parietal cortex). Presentation of emotional distracters during the delay interval evoked strong activity in typical emotional processing regions (amygdala and ventrolateral prefrontal cortex) while simultaneously evoking relative deactivation of the WM regions and impairing WM performance. These results provide the first direct evidence that the detrimental effect of emotional distracters on ongoing cognitive processes entails the interaction between a dorsal neural system associated with "cold" executive processing and a ventral system associated with "hot" emotional processing.

Occipitotemporal Activation Evoked by the Perception of Human Bodies is Modulated by the Presence or Absence of the Face

We investigated the degree to which activation in regions of the brain known to participate in social perception is influenced by the presence or absence of the face and other body parts. Subjects continuously viewed a static image of a lecture hall in which actors appeared briefly in various poses. There were three conditions: Body-Face, in which the actor appeared with limbs, torso, and face clearly visible; Body-Only, in which the actor appeared with his or her face occluded by a book; and Face-Only, in which the actor appeared behind a podium with only face and shoulders visible. Using event-related functional MRI, we obtained strong activation in those regions previously identified as important for face and body perception. These included portions of the fusiform (FFG) and lingual gyri within ventral occipitotemporal cortex (VOTC), and portions of the middle occipital gyrus (corresponding to the previously defined extrastriate body area, or EBA) and posterior superior temporal sulcus (pSTS) within lateral occipitotemporal cortex (LOTC). Activation of the EBA was strongest for the Body-Only condition; indeed, exposing the face decreased EBA activation evoked by the body. In marked contrast, activation in the pSTS was largest when the face was visible, regardless of whether the body was also visible. Activity within the lateral lingual gyrus and adjacent medial FFG was strongest for the Body-Only condition, while activation in the lateral FFG was greatest when both the face and body were visible. These results provide new information regarding the importance of a visible face in both the relative activation and deactivation of brain structures engaged in social perception.

Mood Alters Amygdala Activation to Sad Distractors During an Attentional Task

A behavioral hallmark of mood disorders is biased perception and memory for sad events. The amygdala is poised to mediate internal mood and external event processing because of its connections with both the internal milieu and the sensory world. There is little evidence showing that the amygdala's response to sad sensory stimuli is functionally modulated by mood state, however.

Role of the Inferior Frontal Cortex in Coping with Distracting Emotions

The role of inferior frontal cortex in coping with emotional distracters presented concurrently with a working memory task was investigated using event-related functional magnetic resonance imaging. The study yielded two main findings: (i) processing of emotional distracters was associated with enhanced functional coupling between the amygdala and the inferior frontal cortex and (ii) the inferior frontal cortex showed a left-lateralized activation pattern discriminating successful from unsuccessful trials in the presence of emotional distraction. These findings provide evidence that coping with emotional distraction entails interactions between brain regions responsible for detection and inhibition of emotional distraction, and identified a hemispheric specialization in the inferior frontal cortex in controlling the impact of distracting emotions on cognitive performance (left hemisphere) vs. controlling the subjective feeling of being distracted (right hemisphere).

Guided Saccades Modulate Object and Face-specific Activity in the Fusiform Gyrus

We investigated the influence of saccadic eye movements on the magnitude of functional MRI (fMRI) activation in brain regions known to participate in object and face perception. In separate runs, subjects viewed a static image of a uniform gray field, a face, or a flower. Every 500 ms a small fixation cross made a discrete jump within the image and subjects were required to make a saccade and fixate the cross at its new location. Each run consisted of alternating blocks in which the subject was guided to make small and large saccades. A comparison of large vs. small saccade blocks revealed robust activity in the oculomotor system, particularly within the frontal eye fields (FEF), intraparietal sulcus (IPS), and superior colliculi regardless of the background image. Activity within portions of the ventral occipitotemporal cortex (VOTC) including the lingual and fusiform gyri was also modulated by saccades, but here saccade-related activity was strongly influenced by the background image. Activity within the VOTC was strongest when large saccadic eye movements were made over an image of a face or a flower compared to a uniform gray image. Of most interest was activity in the functionally predefined face-specific region of the fusiform gyrus, where large saccades made over a face increased activity, but where similar large saccades made over a flower or a uniform gray field did not increase activity. These results demonstrate the potentially confounding influence of uncontrolled eye movements for neuroimaging studies of face and object perception.

FMRI Reveals That Involuntary Visual Deviance Processing is Resource Limited

Previous studies suggest that involuntary auditory attention evoked by unattended auditory stimuli is not influenced by the primary focus of attention. However, prior studies from our laboratory have found that processing of unattended auditory deviant tones in the auditory and frontal regions is modulated by top-down attentional demands and resource availability. Whether processing of unattended visual deviant stimuli is altered by the availability of attentional resources has not been established. The goal of the current study was to examine the automaticity of these activations, their modulation by attentional capacity, and the neuroanatomical distribution of any attentional effects upon visual deviance detection. We designed an event-related functional magnetic resonance imaging (fMRI) study during which subjects performed a continuous perceptual-motor-visual tracking task whose difficulty was modulated by changing the control dynamics of a joystick. Changes in the anatomical localization, spatial distribution, and intensity of the blood oxygenation level-dependent (BOLD) response associated with unattended infrequent visual changes were examined during low- and high-difficulty tracking conditions of the primary visual task. Results revealed that the unattended deviants elicited BOLD activation in the visual, fusiform, and parietal regions. In these regions, the intensity and extent of the activation evoked by the deviants decreased as a function of the demands of the primary visual task. These findings suggest that processing of unattended visual deviant stimuli is restricted by the attentional demands of a primary task, as previously demonstrated for unattended auditory deviant tones.

Effect of Bupropion Extended Release on Negative Emotion Processing in Major Depressive Disorder: a Pilot Functional Magnetic Resonance Imaging Study

Prior imaging studies suggest that patients with major depressive disorder have abnormalities in frontal and limbic neural circuitry including the amygdala, which is relatively more activated at rest and in response to negative emotional stimuli (sadness, fear, etc.) in depressed patients than in controls. Concurrently, patients with depression may have decreased activation of attentional executive regions in response to attentional stimuli. This study examined the effect of bupropion XL, an extended release formulation of the nonserotonergic antidepressant agent bupropion, using a paradigm that investigated both negative emotional response and attentional processing.

Regional Brain Differences in the Effect of Distraction During the Delay Interval of a Working Memory Task

Working memory (WM) comprises operations whose coordinated action contributes to our ability to maintain focus on goal-relevant information in the presence of distraction. The present study investigated the nature of distraction upon the neural correlates of WM maintenance operations by presenting task-irrelevant distracters during the interval between the memoranda and probes of a delayed-response WM task. The study used a region of interest (ROIs) approach to investigate the role of anterior (e.g., lateral and medial prefrontal cortex--PFC) and posterior (e.g., parietal and fusiform cortices) brain regions that have been previously associated with WM operations. Behavioral results showed that distracters that were confusable with the memorandum impaired WM performance, compared to either the presence of non-confusable distracters or to the absence of distracters. These different levels of distraction led to differences in the regional patterns of delay interval activity measured with event-related functional magnetic resonance imaging (fMRI). In the anterior ROIs, dorsolateral PFC activation was associated with WM encoding and maintenance, and in maintaining a preparatory state, and ventrolateral PFC activation was associated with the inhibition of distraction. In the posterior ROIs, activation of the posterior parietal and fusiform cortices was associated with WM and perceptual processing, respectively. These findings provide novel evidence concerning the neural systems mediating the cognitive and behavioral responses during distraction, and places frontal cortex at the top of the hierarchy of the neural systems responsible for cognitive control.

Face Processing Without Awareness in the Right Fusiform Gyrus

We investigated brain activity evoked by faces which were not consciously perceived by subjects. Subdural electrophysiological recordings and functional neuroimaging studies have each demonstrated face-specific processing in the fusiform gyrus (FFG) of humans. Using pattern masks, a stimulus can be presented but not consciously perceived, and thus can be used to assay obligatory or automatic processes. Here, using event-related functional magnetic resonance imaging and pattern masking, we observed that masked faces but not masked objects activated the right FFG. Other regions activated by consciously perceived unmasked faces were not activated when faces were masked. These data provide strong evidence for an automatic face-processing region in the right FFG.

Perception of Dynamic Changes in Facial Affect and Identity in Autism

Despite elegant behavioral descriptions of abnormalities for processing emotional facial expressions and biological motion in autism, identification of the neural mechanisms underlying these abnormalities remains a critical and largely unmet challenge. We compared brain activity with dynamic and static facial expressions in participants with and without high-functioning autism using event-related functional magnetic resonance imaging (fMRI) and three classes of face stimuli-emotion morphs (fearful and angry), identity morphs and static images (fearful, angry and neutral). We observed reduced activity in the amygdala (AMY) and fusiform gyrus (FFG) to dynamic emotional expressions in people with autism. There was also a lack of modulation by dynamic compared with static emotional expressions of social brain regions including the AMY, posterior superior temporal sulcus (STS) region and FFG. We observed equivalent emotion and identity morph-evoked activity in participants with and without autism in a region corresponding to the expected location of the more generally motion-sensitive area MT or V5. We conclude that dysfunctions in key components of the human face processing system including the AMY, FFG and posterior STS region are present in individuals with high-functioning autism, and this dysfunction might contribute to the deficits in processing emotional facial expressions.

Controlled Scanpath Variation Alters Fusiform Face Activation

We investigated the influence of experimentally guided saccades and fixations on fMRI activation in brain regions specialized for face and object processing. Subjects viewed a static image of a face while a small fixation cross made a discrete jump within the image every 500 ms. Subjects were required to make a saccade and fixate the cross at its new location. Each run consisted of alternating blocks in which the subject was guided to make a series of saccades and fixations that constituted either a Typical or an Atypical face scanpath. Typical scanpaths were defined as a scanpath in which the fixation cross landed on the eyes or the mouth in 90% of all trials. Atypical scanpaths were defined as scanpaths in which the fixation cross landed on the eyes or mouth on 12% of all trials. The average saccade length was identical in both typical and atypical blocks, and both were preceded by a baseline block where the fixation cross made much smaller jumps in the middle of the screen. Within the functionally predefined face area of the ventral occipitotemporal cortex (VOTC), typical scanpaths evoked significantly more activity when compared to atypical scanpaths. A voxel-based analysis revealed a similar pattern in clusters of voxels located within VOTC, frontal eye fields, superior colliculi, intraparietal sulcus, and inferior frontal gyrus. These results demonstrate that fMRI activation is highly sensitive to the pattern of eye movements employed during face processing, and thus illustrates the potential confounding influence of uncontrolled eye movements for neuroimaging studies of face and object perception in normal and clinical populations.

Unconscious Word Processing Engages a Distributed Network of Brain Regions

A briefly exposed visual stimulus may not be consciously perceived if it is preceded and followed by a dissimilar visual pattern or mask. Despite the subject's lack of awareness, prior behavioral studies have shown that such masked stimuli, nevertheless, engage domain-specific processes [Dehaene, S., Naccache, L., Cohen, L., Le Bihan, D., Mangin, J.-F., Poline, J.-B., et al. Cerebral mechanisms of word masking and unconscious repetition priming. Nature Neuroscience, 4, 752-758, 2001; Bar, M., & Biederman, I. Subliminal visual priming. Psychological Science, 9, 464-469, 1998; Dehaene, S., Naccache, L., Le Clec'H, G., Koechlin, E., Mueller, M., Dehaene-Lambertz, G., et al. Imaging unconscious semantic priming. Nature, 395, 597-600, 1998; Whalen, P. J., Rauch, S. L., Etcoff, N. L., McInerney, S. C., Lee, M. B., & Jenike, M. A. Masked presentations of emotional facial expressions modulate amygdala activity without explicit knowledge. Journal of Neuroscience, 18, 411-418, 1998; Marcel, A. J. Conscious and unconscious perception: Experiments on visual masking and word recognition. Cognitive Psychology, 15, 197-237, 1983]. Masking thus provides a method for identifying language processes that are preattentive and automatic. Functional magnetic resonance imaging used in concert with masking may identify brain regions engaged by these unconscious language processes. In an adaptation design, subjects viewed a continuous stream of masked words and masked nonwords while performing an unrelated detection task, in which they were asked to make a response to a visible colored nonword stimulus (i.e., ampersands in red or blue font). Most trials were masked nonwords and masked words were presented once every 12-15 sec. The task ensured participant engagement, while the masked nonword baseline controlled for perceptual and orthographic processing. Participants were naïve to the purpose of the experiment and testing indicated that they did not consciously perceive either the words or nonwords. Masked words, but not masked nonwords, strongly activated left hemisphere language regions, including Broca's area, the angular gyrus, and the lateral temporal lobe. Differential activation of the posterior corpus callosum was also observed.

Neural Systems for Executive and Emotional Processing Are Modulated by Symptoms of Posttraumatic Stress Disorder in Iraq War Veterans

The symptom-provocation paradigms generally used in neuroimaging studies of posttraumatic stress disorder (PTSD) have placed high demands on emotion processing but lacked cognitive processing, thereby limiting the ability to assess alterations in neural systems that subserve executive functions and their interactions with emotion processing. Thirty-nine veterans from Iraq and Afghanistan underwent functional magnetic resonance imaging while exposed to emotional combat-related and neutral civilian scenes interleaved with an executive processing task. Contrast activation maps were regressed against PTSD symptoms as measured by the Davidson Trauma Scale. Activation for emotional compared with neutral stimuli was highly positively correlated with level of PTSD symptoms in ventral frontolimbic regions, notably the ventromedial prefrontal cortex, inferior frontal gyrus, and ventral anterior cingulate gyrus. Conversely, activation for the executive task was negatively correlated with PTSD symptoms in the dorsal executive network, notably the middle frontal gyrus, dorsal anterior cingulate gyrus, and inferior parietal lobule. Thus, there is a strong link between the subjectively assessed behavioral phenomenology of PTSD and objective neurobiological markers. These findings extend the largely symptom provocation-based functional neuroanatomy to provide evidence that interrelated executive and emotional processing systems of the brain are differentially affected by PTSD symptomatology in recently deployed war veterans.

Guided Saccades Modulate Face- and Body-sensitive Activation in the Occipitotemporal Cortex During Social Perception

Functional magnetic resonance imaging (fMRI) has identified distinct brain regions in ventral occipitotemporal cortex (VOTC) and lateral occipitotemporal cortex (LOTC) that are differentially activated by pictures of faces and bodies. Recent work from our laboratory has shown that the strong LOTC activation evoked by bodies in which the face is occluded is attenuated when the occlusion is removed. We hypothesized that this attenuation may occur because subjects preferentially fixate upon faces when present in the scene. Here, we experimentally manipulated subjects' fixations while they viewed a static picture of a character whose face, hand, and torso were continuously visible throughout each run. The subject's saccades and fixations were guided by a small fixation cross that made discrete jumps to a new location every 500ms. Subjects were instructed to follow the fixation cross and make a button press whenever it changed size. In a series of blocks, the fixation cross shifted from locations on the face, on the hand, and to locations on a background image of a phase-scrambled face. In a second study, the fixation cross moved similarly, but the hand locations were changed to locations along the character's body or torso. A localizer task was used to identify face- and body-sensitive regions of LOTC. Body-sensitive regions were strongly activated when the subjects' saccades were guided over the character's torso relative to when the saccades were guided over the character's face. Little to no activity occurred in the body-sensitive region of LOTC when the subjects' saccades were guided over the character's hand. The localizer task was unable to differentiate body-sensitive regions in lateral VOTC from face-sensitive regions, or body-sensitive regions in medial VOTC from flower-sensitive regions. Guided saccades over the body strongly activated both lateral and medial VOTC. These results provide new insights into the function of body-sensitive visual areas in both LOTC and VOTC, and illustrate the potential confounding influence of uncontrolled eye movements for neuroimaging studies of social perception.

Depressive State- and Disease-related Alterations in Neural Responses to Affective and Executive Challenges in Geriatric Depression

Geriatric depression has been associated with a heterogeneous neuropathology. Identifying both depressive state-related and disease-related alterations in brain regions associated with emotion and cognitive function could provide useful diagnostic information in geriatric depression.

Prefrontal Mechanisms for Executive Control over Emotional Distraction Are Altered in Major Depression

A dysfunction in the interaction between executive function and mood regulation has been proposed as the pathophysiology of depression. However, few studies have investigated the alteration in brain systems related to executive control over emotional distraction in depression. To address this issue, 19 patients with major depressive disorder (MDD) and 20 healthy controls were scanned using functional magnetic resonance imaging. Participants performed an emotional oddball task in which infrequently presented circle targets required detection while sad and neutral pictures were irrelevant novel distractors. Hemodynamic responses were compared for targets, sad distractors, and for targets that followed sad or neutral distractors (Target-after-Sad and Target-after-Neutral). Patients with MDD revealed attenuated activation overall to targets in executive brain regions. Behaviorally, MDD patients were slower in response to Target-after-Sad than Target-after-Neutra stimuli. Patients also revealed a reversed activation pattern from controls in response to this contrast in the left anterior cingulate, insula, right inferior frontal gyrus (IFG), and bilateral middle frontal gyrus. Those patients who engaged the right IFG more during Target-after-Neutral stimuli responded faster to targets, confirming a role of this region in coping with emotional distraction. The results provide direct evidence of an alteration in the neural systems that interplay cognition with mood in MDD.

Perceived Causality Influences Brain Activity Evoked by Biological Motion

Using functional magnetic resonance imaging (fMRI), we investigated brain activity in an observer who watched the hand and arm motions of an individual when that individual was, or was not, the cause of the motion. Subjects viewed a realistic animated 3D character who sat at a table containing four pistons. On Intended Motion trials, the character raised his hand and arm upwards. On Unintended Motion trials, the piston under one of the character's hands pushed the hand and arm upward with the same motion. Finally, during Non-Biological Motion control trials, a piston pushed a coffee mug upward in the same smooth motion. Hand and arm motions, regardless of intention, evoked significantly more activity than control trials in a bilateral region that extended ventrally from the posterior superior temporal sulcus (pSTS) region and which was more spatially extensive in the right hemisphere. The left pSTS near the temporal-parietal junction, robustly differentiated between the Intended Motion and Unintended Motion conditions. Here, strong activity was observed for Intended Motion trials, while Unintended Motion trials evoked similar activity as the coffee mug trials. Our results demonstrate a strong hemispheric bias in the role of the pSTS in the perception of causality of biological motion.

Opposing Influences of Emotional and Non-emotional Distracters Upon Sustained Prefrontal Cortex Activity During a Delayed-response Working Memory Task

Performance in delayed-response working memory (WM) tasks is typically associated with sustained activation in the dorsolateral prefrontal cortex (dlPFC) that spans the delay between the memoranda and the memory probe. Recent studies have demonstrated that novel distracters presented during the delay interval both affect sustained activation and impair WM performance. However, the effect of the performance-impairing distracters upon sustained dlPFC delay activity was related to the characteristics of the distracters: memoranda-confusable distracters increased delay activity, whereas memoranda-nonconfusable emotional distracters decreased delay activity. Because these different effects were observed in different studies, it is possible that different dlPFC regions were involved and the paradox is more apparent than real. To investigate this possibility, event-related fMRI data were recorded while subjects performed a WM task for faces with memoranda-confusable (novel faces) and memoranda-nonconfusable emotional (novel scenes) distracters presented during the delay interval. Consistent with previous findings, confusable face distracters increased dlPFC delay activity, while nonconfusable emotional distracters decreased dlPFC delay activity, and these opposing effects modulated activity in the same dlPFC regions. These results provide direct evidence that specific regions of the dlPFC are generally involved in mediating the effects of distraction, while showing sensitivity to the nature of distraction. These findings are relevant for understanding alterations in the neural mechanisms associated with both general impairment of cognitive control and with specific impairment in the ability to control emotional distraction, such as those observed in aging and affective disorders, respectively.

The Role of Trauma-related Distractors on Neural Systems for Working Memory and Emotion Processing in Posttraumatic Stress Disorder

The relevance of emotional stimuli to threat and survival confers a privileged role in their processing. In PTSD, the ability of trauma-related information to divert attention is especially pronounced. Information unrelated to the trauma may also be highly distracting when it shares perceptual features with trauma material. Our goal was to study how trauma-related environmental cues modulate working memory networks in PTSD. We examined neural activity in participants performing a visual working memory task while distracted by task-irrelevant trauma and non-trauma material. Recent post-9/11 veterans were divided into a PTSD group (n=22) and a trauma-exposed control group (n=20) based on the Davidson trauma scale. Using fMRI, we measured hemodynamic change in response to emotional (trauma-related) and neutral distraction presented during the active maintenance period of a delayed-response working memory task. The goal was to examine differences in functional networks associated with working memory (dorsolateral prefrontal cortex and lateral parietal cortex) and emotion processing (amygdala, ventrolateral prefrontal cortex, and fusiform gyrus). The PTSD group showed markedly different neural activity compared to the trauma-exposed control group in response to task-irrelevant visual distractors. Enhanced activity in ventral emotion processing regions was associated with trauma distractors in the PTSD group, whereas activity in brain regions associated with working memory and attention regions was disrupted by distractor stimuli independent of trauma content. Neural evidence for the impact of distraction on working memory is consistent with PTSD symptoms of hypervigilance and general distractibility during goal-directed cognitive processing.

A Comparison of Automated Segmentation and Manual Tracing for Quantifying Hippocampal and Amygdala Volumes

Large databases of high-resolution structural MR images are being assembled to quantitatively examine the relationships between brain anatomy, disease progression, treatment regimens, and genetic influences upon brain structure. Quantifying brain structures in such large databases cannot be practically accomplished by expert neuroanatomists using hand-tracing. Rather, this research will depend upon automated methods that reliably and accurately segment and quantify dozens of brain regions. At present, there is little guidance available to help clinical research groups in choosing such tools. Thus, our goal was to compare the performance of two popular and fully automated tools, FSL/FIRST and FreeSurfer, to expert hand tracing in the measurement of the hippocampus and amygdala. Volumes derived from each automated measurement were compared to hand tracing for percent volume overlap, percent volume difference, across-sample correlation, and 3-D group-level shape analysis. In addition, sample size estimates for conducting between-group studies were computed for a range of effect sizes. Compared to hand tracing, hippocampal measurements with FreeSurfer exhibited greater volume overlap, smaller volume difference, and higher correlation than FIRST, and sample size estimates with FreeSurfer were closer to hand tracing. Amygdala measurement with FreeSurfer was also more highly correlated to hand tracing than FIRST, but exhibited a greater volume difference than FIRST. Both techniques had comparable volume overlap and similar sample size estimates. Compared to hand tracing, a 3-D shape analysis of the hippocampus showed FreeSurfer was more accurate than FIRST, particularly in the head and tail. However, FIRST more accurately represented the amygdala shape than FreeSurfer, which inflated its anterior and posterior surfaces.

Brain-performance Correlates of Working Memory Retrieval in Schizophrenia: a Cognitive Modeling Approach

Correlations of cognitive functioning with brain activation during a sternberg item recognition paradigm (SIRP) were investigated in patients with schizophrenia and in healthy controls studied at 8 sites. To measure memory scanning times, 4 response time models were fit to SIRP data. The best fitting model assumed exhaustive serial memory scanning followed by self-terminating memory search and involved one intercept parameter to represent SIRP processes not contributing directly to memory scanning. Patients displayed significantly longer response times with increasing memory load and differed on the memory scanning, memory search, and intercept parameters of the best fitting probability model. Groups differed in the correlation between the memory scanning parameter and linear brain response to increasing memory load within left inferior and left middle frontal gyrus, bilateral caudate, and right precuneus. The pattern of findings in these regions indicated that high scanning capacity was associated with high neural capacity among healthy subjects but that scanning speed was uncoupled from brain response to increasing memory load among schizophrenia patients. Group differences in correlation of the best fitting model's scanning parameter with a quadratic trend in brain response to increasing memory load suggested inefficient or disordered patterns of neural inhibition among individuals with schizophrenia, especially in the left perirhinal and entorhinal cortices. The results show at both cognitive and neural levels that disordered memory scanning contributes to deficient SIRP performance among schizophrenia patients.

Alterations in the Neural Circuitry for Emotion and Attention Associated with Posttraumatic Stress Symptomatology

Information processing models of posttraumatic stress disorder (PTSD) suggest that PTSD is characterized by preferential allocation of attentional resources to potentially threatening stimuli. However, few studies have examined the neural pattern underlying attention and emotion in association with PTSD symptomatology. In the present study, combat veterans with PTSD symptomatology engaged in an emotional oddball task while undergoing functional magnetic resonance imaging (fMRI). Veterans were classified into a high or low symptomatology group based on their scores on the Davidson Trauma Scale (DTS). Participants discriminated infrequent target stimuli (circles) from frequent standards (squares) while emotional and neutral distractors were presented infrequently and irregularly. Results revealed that participants with greater PTSD symptomatology showed enhanced neural activity in ventral-limbic and dorsal regions for emotional stimuli and attenuated activity in dorsolateral prefrontal and parietal regions for attention targets. In the anterior cingulate gyrus, participants with fewer PTSD symptoms showed equivalent responses to attentional and emotional stimuli while the high symptom group showed greater activation for negative emotional stimuli. Taken together, the results suggest that hyperresponsive ventral-limbic activity coupled with altered dorsal-attention and anterior cingulate function may be a neural marker of attention bias in PTSD.

A Comparison of Brain Activity Evoked by Single Content and Function Words: an FMRI Investigation of Implicit Word Processing

Content and function words have different roles in language and differ greatly in their semantic content. Although previous research has suggested that these different roles may be mediated by different neural substrates, the neuroimaging literature on this topic is particularly scant. Moreover, fMRI studies that have investigated differences between content and function words have utilized tasks that focus the subjects' attention on the differences between these word types. It is possible, then, that task-related differences in attention, working memory, and decision-making contribute to the differential patterns of activation observed. Here, subjects were engaged in a continuous working memory cover task while single, task-irrelevant content and function words were infrequently and irregularly presented. Nonword letter strings were displayed in black font at a fast rate (2/s). Subjects were required to either remember or retrieve occasional nonwords that were presented in colored fonts. Incidental and irrelevant to the memory task, content and function words were interspersed among nonwords at intervals of 12 to 15 s. Both word types strongly activated temporal-parietal cortex, middle and anterior temporal cortex, inferior frontal gyrus, parahippocampal gyrus, and orbital frontal cortex. Activations were more extensive in the left hemisphere. Content words elicited greater activation than function words in middle and anterior temporal cortex, a sub-region of orbital frontal cortex, and the parahippocampal region. Words also evoked extensive deactivation, most notably in brain regions previously associated with working memory and attention.

The Relation Between Race-related Implicit Associations and Scalp-recorded Neural Activity Evoked by Faces from Different Races

The neural correlates of the perception of faces from different races were investigated. White participants performed a gender identification task in which Asian, Black, and White faces were presented while event-related potentials (ERPs) were recorded. Participants also completed an implicit association task for Black (IAT-Black) and Asian (IAT-Asian) faces. ERPs evoked by Black and White faces differed, with Black faces evoking a larger positive ERP that peaked at 168 ms over the frontal scalp, and White faces evoking a larger negative ERP that peaked at 244 ms. These Black/White ERP differences significantly correlated with participants' scores on the IAT-Black. ERPs also differentiated White from Asian faces and a significant correlation was obtained between the White-Asian ERP difference waves at approximately 500 ms and the IAT-Asian. A positive ERP at 116 ms over occipital scalp differentiated all three races, but was not correlated with either IAT. In addition, a late positive component (around 592 ms) was greater for the same race compared to either other race faces, suggesting potentially more extended or deeper processing of the same race faces. Taken together, the ERP/IAT correlations observed for both other races indicate the influence of a race-sensitive evaluative process that may include early more automatic and/or implicit processes and relatively later more controlled processes.

Rebuttal to Hasan and Pedraza in Comments and Controversies: "Improving the Reliability of Manual and Automated Methods for Hippocampal and Amygdala Volume Measurements"

Here we address the critiques offered by Hasan and Pedraza to our recently published manuscript comparing the performance of two automated segmentation programs, FSL/FIRST and FreeSurfer (Morey R, Petty C, Xu Y, Pannu Hayes J, Wagner H, Lewis D, LaBar K, Styner M, McCarthy G. (2009): A comparison of automated segmentation and manual tracing for quantifying of hippocampal and amygdala volumes. Neuroimage 45:855-866). We provide an assessment and discussion of their specific critiques. Hasan and Pedraza bring up some important points concerning our omission of sample demographic features and inclusion of left and right hemisphere volumes as independent measures in correlational analyses. We present additional data on demographic attributes of our sample and correlations analyzed separately on left and right hemispheres of the amygdala and hippocampus. While their commentary aids the reader to more critically asses our study, it falls short of substantiating that our omissions ought to lead readers to significantly revise their interpretations. Further research will help to disentangle the advantages and limitations of the various freely-available automated segmentation software packages.

The Effect of Acute Tryptophan Depletion on Emotional Distraction and Subsequent Memory

Serotonin is a key neurotransmitter involved in emotional regulation and memory. A number of studies using acute tryptophan depletion (ATD) in healthy subjects have shown that a temporary serotonin reduction both induces a negative emotional bias and impairs long-term memory. However, little is known about the specific effects of ATD on emotional memory. Using functional magnetic resonance imaging (fMRI), we investigated the effect of ATD on negative memory and executive function in healthy volunteers. Our emotional oddball task required participants to distinguish infrequently presented targets from distracting negative and neutral pictures. Memory for the distracting pictures was tested 1 h following the fMRI session. ATD selectively enhanced memory for negative distractors relative to neutral distractors and increased activation in response to the negative distractors in the left orbital-inferior frontal, dorsomedial prefrontal and bilateral angular gyri. ATD also induced greater activation in the left inferior frontal gyrus and anterior cingulate across all stimuli. Stronger frontal activation to distractors was positively correlated with memory performance on ATD but not control days, indicating a possible compensatory mechanism for coping with increased task demand under the ATD challenge. These findings highlight the importance of serotonin in negative memory with implications for mood disorders.

Reading About the Actions of Others: Biological Motion Imagery and Action Congruency Influence Brain Activity

Prior neuroimaging research has implicated regions within and near the posterior superior temporal sulcus (pSTS) in the visual processing of biological motion and of the intentions implied by specific movements. However, it is unknown whether this region is engaged during the processing of human motion at a conceptual level, such as during story comprehension. Here, we obtained functional magnetic resonance images from subjects reading brief stories that described a human character's background and then concluded with an action or decision made by the character. Half of the stories contained incidental descriptions of biological motion (such as the character's walking or grasping) while the remaining half did not. As a second factor, the final action of the story was either congruent or incongruent with the character's background and implied goals and intentions. Stories that contained biological motion strongly activated the pSTS bilaterally, along with ventral temporal areas, premotor cortex, left motor cortex, and the precuneus. Active regions of pSTS in individual subjects closely overlapped with regions identified with a separate biological motion localizer (point-light display) task. Reading incongruent versus congruent stories activated dorsal anterior cingulate cortex and bilateral anterior insula. These results support the hypothesis that reading can engage higher visual cortex in a content-specific manner, and suggest that the presence of biological motion should be controlled as a potential confound in fMRI studies using story comprehension tasks.

Scan-rescan Reliability of Subcortical Brain Volumes Derived from Automated Segmentation

Large-scale longitudinal studies of regional brain volume require reliable quantification using automated segmentation and labeling. However, repeated MR scanning of the same subject, even if using the same scanner and acquisition parameters, does not result in identical images due to small changes in image orientation, changes in prescan parameters, and magnetic field instability. These differences may lead to appreciable changes in estimates of volume for different structures. This study examined scan-rescan reliability of automated segmentation algorithms for measuring several subcortical regions, using both within-day and across-day comparison sessions in a group of 23 normal participants. We found that the reliability of volume measures including percent volume difference, percent volume overlap (Dice's coefficient), and intraclass correlation coefficient (ICC), varied substantially across brain regions. Low reliability was observed in some structures such as the amygdala (ICC = 0.6), with higher reliability (ICC = 0.9) for other structures such as the thalamus and caudate. Patterns of reliability across regions were similar for automated segmentation with FSL/FIRST and FreeSurfer (longitudinal stream). Reliability was associated with the volume of the structure, the ratio of volume to surface area for the structure, the magnitude of the interscan interval, and the method of segmentation. Sample size estimates for detecting changes in brain volume for a range of likely effect sizes also differed by region. Thus, longitudinal research requires a careful analysis of sample size and choice of segmentation method combined with a consideration of the brain structure(s) of interest and the magnitude of the anticipated effects.

Selective Attention Modulates Face-specific Induced Gamma Oscillations Recorded from Ventral Occipitotemporal Cortex

EEG studies from subdural electrodes have demonstrated a face-specific event-related potential (face-N200) recorded from human ventral occipitotemporal cortex. The insensitivity of face-N200 to task manipulations has supported the proposal that face-N200 reflects an initial obligatory response to faces. This result stands in striking contrast to results of neuroimaging studies that have demonstrated strong task sensitivity of the fusiform hemodynamic response evoked by faces, and thus has created a paradox in the face perception literature. We recorded field potentials directly from the cortical surface of 16 patients while they selectively attended to faces or houses. Here we report that face-specific gamma activity recorded at face-N200 sites is strongly modulated by selective attention, while face-N200 is not. Our results reconcile prior electrophysiological and hemodynamic studies of face perception, and suggest that attentional modulation of the face response follows an initial phase that is largely insensitive to attention.

Attentional Facilitation Throughout Human Visual Cortex Lingers in Retinotopic Coordinates After Eye Movements

With each eye movement, the image of the world received by the visual system changes dramatically. To maintain stable spatiotopic (world-centered) visual representations, the retinotopic (eye-centered) coordinates of visual stimuli are continually remapped, even before the eye movement is completed. Recent psychophysical work has suggested that updating of attended locations occurs as well, although on a slower timescale, such that sustained attention lingers in retinotopic coordinates for several hundred milliseconds after each saccade. To explore where and when this "retinotopic attentional trace" resides in the cortical visual processing hierarchy, we conducted complementary functional magnetic resonance imaging and event-related potential (ERP) experiments using a novel gaze-contingent task. Human subjects executed visually guided saccades while covertly monitoring a fixed spatiotopic target location. Although subjects responded only to stimuli appearing at the attended spatiotopic location, blood oxygen level-dependent responses to stimuli appearing after the eye movement at the previously, but no longer, attended retinotopic location were enhanced in visual cortical area V4 and throughout visual cortex. This retinotopic attentional trace was also detectable with higher temporal resolution in the anterior N1 component of the ERP data, a well established signature of attentional modulation. Together, these results demonstrate that, when top-down spatiotopic signals act to redirect visuospatial attention to new retinotopic locations after eye movements, facilitation transiently persists in the cortical regions representing the previously relevant retinotopic location.

A Novel Method for Quantifying Scanner Instability in FMRI

A method was developed to quantify the effect of scanner instability on functional MRI data by comparing the instability noise to endogenous noise present when scanning a human. The instability noise was computed from agar phantom data collected with two flip angles, allowing for a separation of the instability from the background noise. This method was used on human data collected at four 3 T scanners, allowing the physiological noise level to be extracted from the data. In a "well-operating" scanner, the instability noise is generally less than 10% of physiological noise in white matter and only about 2% of physiological noise in cortex. This indicates that instability in a well-operating scanner adds very little noise to functional MRI results. This new method allows researchers to make informed decisions about the maximum instability level a scanner can have before it is taken off line for maintenance or rejected from a multisite consortium. This method also provides information about the background noise, which is generally larger in magnitude than the instability noise. Magn Reson Med, 2010. © 2010 Wiley-Liss, Inc.

Face-Specific Resting Functional Connectivity Between the Fusiform Gyrus and Posterior Superior Temporal Sulcus

Faces activate specific brain regions in fMRI, including the fusiform gyrus (FG) and the posterior superior temporal sulcus (pSTS). The fact that the FG and pSTS are frequently co-activated suggests that they may interact synergistically in a distributed face processing network. Alternatively, the functions implemented by these regions may be encapsulated from each other. It has proven difficult to evaluate these two accounts during visual processing of face stimuli. However, if the FG and pSTS interact during face processing, the substrate for such interactions may be apparent in a correlation of the BOLD timeseries from these two regions during periods of rest when no faces are present. To examine face-specific resting correlations, we developed a new partial functional connectivity approach in which we removed variance from the FG that was shared with other category-selective and control regions. The remaining face-specific FG resting variance was then used to predict resting signals throughout the brain. In two experiments, we observed face-specific resting functional connectivity between FG and pSTS, and importantly, these correlations overlapped precisely with the face-specific pSTS region obtained from independent localizer runs. Additional region-of-interest and pattern analyses confirmed that the FG-pSTS resting correlations were face-specific. These findings support a model in which face processing is distributed among a finite number of connected, but nevertheless face-specialized regions. The discovery of category-specific interactions in the absence of visual input suggests that resting networks may provide a latent foundation for task processing.

Staying Cool when Things Get Hot: Emotion Regulation Modulates Neural Mechanisms of Memory Encoding

During times of emotional stress, individuals often engage in emotion regulation to reduce the experiential and physiological impact of negative emotions. Interestingly, emotion regulation strategies also influence memory encoding of the event. Cognitive reappraisal is associated with enhanced memory while expressive suppression is associated with impaired explicit memory of the emotional event. However, the mechanism by which these emotion regulation strategies affect memory is unclear. We used event-related fMRI to investigate the neural mechanisms that give rise to memory formation during emotion regulation. Twenty-five participants viewed negative pictures while alternately engaging in cognitive reappraisal, expressive suppression, or passive viewing. As part of the subsequent memory design, participants returned to the laboratory two weeks later for a surprise memory test. Behavioral results showed a reduction in negative affect and a retention advantage for reappraised stimuli relative to the other conditions. Imaging results showed that successful encoding during reappraisal was uniquely associated with greater co-activation of the left inferior frontal gyrus, amygdala, and hippocampus, suggesting a possible role for elaborative encoding of negative memories. This study provides neurobehavioral evidence that engaging in cognitive reappraisal is advantageous to both affective and mnemonic processes.

The Wolfpack Effect. Perception of Animacy Irresistibly Influences Interactive Behavior

Imagine a pack of predators stalking their prey. The predators may not always move directly toward their target (e.g., when circling around it), but they may be consistently facing toward it. The human visual system appears to be extremely sensitive to such situations, even in displays involving simple shapes. We demonstrate this by introducing the wolfpack effect, which is found when several randomly moving, oriented shapes (darts, or discs with "eyes") consistently point toward a moving disc. Despite the randomness of the shapes' movement, they seem to interact with the disc--as if they are collectively pursuing it. This impairs performance in interactive tasks (including detection of actual pursuit), and observers selectively avoid such shapes when moving a disc through the display themselves. These and other results reveal that the wolfpack effect is a novel "social" cue to perceived animacy. And, whereas previous work has focused on the causes of perceived animacy, these results demonstrate its effects, showing how it irresistibly and implicitly shapes visual performance and interactive behavior.

The Posterior Superior Temporal Sulcus is Sensitive to the Outcome of Human and Non-human Goal-directed Actions

Prior studies have demonstrated that the posterior superior temporal sulcus (pSTS) is involved in analyzing the intentions underlying actions and is sensitive to the context within which actions occur. However, it is debated whether the pSTS is actually sensitive to goals underlying actions, or whether previous studies can be interpreted to suggest that the pSTS is instead involved in the allocation of visual attention towards unexpected events. In addition, little is known about whether the pSTS is specialized for reasoning about the actions of social agents or whether the pSTS is sensitive to the actions of both animate and inanimate entities. Here, using functional magnetic resonance imaging, we investigated activation in response to passive viewing of successful and unsuccessful animate and inanimate goal-directed actions. Activation in the right pSTS was stronger in response to failed actions compared to successful actions, suggesting that the pSTS plays a role in encoding the goals underlying actions. Activation in the pSTS did not differentiate between animate and inanimate actions, suggesting that the pSTS is sensitive to the goal-directed actions of both animate and inanimate entities.

Goal-Directed Actions Activate the Face-Sensitive Posterior Superior Temporal Sulcus and Fusiform Gyrus in the Absence of Human-Like Perceptual Cues

The conditions under which we identify entities as animate agents and the neural mechanisms supporting this ability are central questions in social neuroscience. Prior studies have focused upon 2 perceptual cues for signaling animacy: 1) surface features representing body forms such as faces, torsos, and limbs and 2) motion cues associated with biological forms. Here, we consider a third cue-the goal-directedness of an action. Regions in the social brain network, such as the right posterior superior temporal sulcus (pSTS) and fusiform face area (FFA), are activated by human-like motion and body form perceptual cues signaling animacy. Here, we investigate whether these same brain regions are activated by goal-directed motion even when performed by entities that lack human-like perceptual cues. We observed an interaction effect whereby the presence of either human-like perceptual cues or goal-directed actions was sufficient to activate the right pSTS and FFA. Only stimuli that lacked human-like perceptual cues and goal-directed actions failed to activate the pSTS and FFA at the same level.

The Influence of Emotional Distraction on Verbal Working Memory: an FMRI Investigation Comparing Individuals with Schizophrenia and Healthy Adults

The ability to maintain information over short periods of time (i.e., working memory) is critically important in a variety of cognitive functions including language, planning, and decision-making. Recent functional Magnetic Resonance Imaging (fMRI) research with healthy adults has shown that brain activations evoked during the delay interval of working memory tasks can be reduced by the presentation of distracting emotional events, suggesting that emotional events may take working-memory processes momentarily offline. Both executive function and emotional processing are disrupted in schizophrenia, and here we sought to elucidate the effect of emotional distraction upon brain activity in schizophrenic and healthy adults performing a verbal working memory task. During the delay period between the memoranda and memory probe items, emotional and neutral distractors differentially influenced brain activity in these groups. In healthy adults, the hemodynamic response from posterior cingulate, orbital frontal cortex, and the parietal lobe strongly differentiated emotional from neutral distractors. In striking contrast, schizophrenic adults showed no significant differences in brain activation when processing emotional and neutral distractors. Moreover, the influence of emotional distractors extended into the memory probe period in healthy, but not schizophrenic, adults. The results suggest that although emotional items are highly salient for healthy adults, emotional items are no more distracting than neutral ones to individuals with schizophrenia.

A Novel Method for Quantifying Scanner Instability in FMRI

A method was developed to quantify the effect of scanner instability on functional MRI data by comparing the instability noise to endogenous noise present when scanning a human. The instability noise was computed from agar phantom data collected with two flip angles, allowing for a separation of the instability from the background noise. This method was used on human data collected at four 3 T scanners, allowing the physiological noise level to be extracted from the data. In a "well-operating" scanner, the instability noise is generally less than 10% of physiological noise in white matter and only about 2% of physiological noise in cortex. This indicates that instability in a well-operating scanner adds very little noise to functional MRI results. This new method allows researchers to make informed decisions about the maximum instability level a scanner can have before it is taken off line for maintenance or rejected from a multisite consortium. This method also provides information about the background noise, which is generally larger in magnitude than the instability noise.

Serotonin Transporter Gene Polymorphisms and Brain Function During Emotional Distraction from Cognitive Processing in Posttraumatic Stress Disorder

Serotonergic system dysfunction has been implicated in posttraumatic stress disorder (PTSD). Genetic polymorphisms associated with serotonin signaling may predict differences in brain circuitry involved in emotion processing and deficits associated with PTSD. In healthy individuals, common functional polymorphisms in the serotonin transporter gene (SLC6A4) have been shown to modulate amygdala and prefrontal cortex (PFC) activity in response to salient emotional stimuli. Similar patterns of differential neural responses to emotional stimuli have been demonstrated in PTSD but genetic factors influencing these activations have yet to be examined.

Multisite Reliability of Cognitive BOLD Data

Investigators perform multi-site functional magnetic resonance imaging studies to increase statistical power, to enhance generalizability, and to improve the likelihood of sampling relevant subgroups. Yet undesired site variation in imaging methods could off-set these potential advantages. We used variance components analysis to investigate sources of variation in the blood oxygen level-dependent (BOLD) signal across four 3-T magnets in voxelwise and region-of-interest (ROI) analyses. Eighteen participants traveled to four magnet sites to complete eight runs of a working memory task involving emotional or neutral distraction. Person variance was more than 10 times larger than site variance for five of six ROIs studied. Person-by-site interactions, however, contributed sizable unwanted variance to the total. Averaging over runs increased between-site reliability, with many voxels showing good to excellent between-site reliability when eight runs were averaged and regions of interest showing fair to good reliability. Between-site reliability depended on the specific functional contrast analyzed in addition to the number of runs averaged. Although median effect size was correlated with between-site reliability, dissociations were observed for many voxels. Brain regions where the pooled effect size was large but between-site reliability was poor were associated with reduced individual differences. Brain regions where the pooled effect size was small but between-site reliability was excellent were associated with a balance of participants who displayed consistently positive or consistently negative BOLD responses. Although between-site reliability of BOLD data can be good to excellent, acquiring highly reliable data requires robust activation paradigms, ongoing quality assurance, and careful experimental control.

The Relationship of Gamma Oscillations and Face-specific ERPs Recorded Subdurally from Occipitotemporal Cortex

The perception of faces evokes characteristic electrophysiological responses at discrete loci in human fusiform gyrus and adjacent ventral occipitotemporal cortical sites. Prominent among these responses are a surface-negative potential at ∼200-ms postonset (face-N200) and face-induced spectral perturbations in the gamma band (face-γERSP). The degree to which these responses represent activity in the same cortical loci and the degree to which they are influenced by the same perceptual and task variables are unknown. We evaluated this anatomical colocalization and functional correlation in 2 experiments in which the electrocorticogram was recorded from subdural electrodes in 51 participants. Experiment 1 investigated the category specificity of the γERSP and its colocalization with the face-N200. Experiment 2 examined differences in face-N200 and face-γERSP to face stimuli that varied in featural complexity. We found that γERSP is a category-specific phenomenon with separate, though overlapping, category sensitivities as the N200. Further, the presence of face-γERSP at an electrode site significantly predicted the presence and amplitude of face-N200 at that site. However, the converse was not true in that face-N200 was evoked by impoverished face stimuli that did not induce face-γERSP. These results demonstrate that these electrophysiological responses reflect separate components of the brain's face processing system.

Electrophysiological Correlates of Processing Faces of Younger and Older Individuals

The 'own-age bias' in face processing suggests that the age of a face constitutes one important factor that influences attention to and memory for faces. The present experiment investigated electrophysiological correlates of processing faces of younger and older individuals. Younger participants were presented with pictures of unfamiliar younger and older faces in the context of a gender categorization task. A comparison of event-related potentials showed that early components are sensitive to faces of different ages: (i) larger positive potential peaking at 160 ms (P200) for older than younger faces at fronto-central electrodes; (ii) larger negative potential peaking at 252 ms (N200) for younger than older faces at fronto-central electrodes; (iii) larger negative-going deflection peaking at 320 ms (N250) for younger than older faces at occipito-temporal electrodes; and (iv) larger late positive potential peaking at 420 ms (LPP 420) for older than younger faces at parietal and other electrodes. We discuss similarities between the present study and a previously published study of faces of different races as suggesting involvement of comparable electrophysiological responses when differentiating between stimulus categories.

Reduced Hippocampal and Amygdala Activity Predicts Memory Distortions for Trauma Reminders in Combat-related PTSD

Neurobiological models of posttraumatic stress disorder (PTSD) suggest that altered activity in the medial temporal lobes (MTL) during encoding of traumatic memories contribute to the development and maintenance of the disorder. However, there is little direct evidence in the PTSD literature to support these models. The goal of the present study was to examine MTL activity during trauma encoding in combat veterans using the subsequent memory paradigm. Fifteen combat veterans diagnosed with PTSD and 14 trauma-exposed control participants viewed trauma-related and neutral pictures while undergoing event-related fMRI. Participants returned one week after scanning for a recognition memory test. Region-of-interest (ROI) and voxel-wise whole brain analyses were conducted to examine the neural correlates of successful memory encoding. Patients with PTSD showed greater false alarm rates for novel lures than the trauma-exposed control group, suggesting reliance on gist-based representations in lieu of encoding contextual details. Imaging analyses revealed reduced activity in the amygdala and hippocampus in PTSD patients during successful encoding of trauma-related stimuli. Reduction in left hippocampal activity was associated with high arousal symptoms on the Clinician-Administered PTSD Scale (CAPS). The behavioral false alarm rate for traumatic stimuli co-varied with activity in the bilateral precuneus. These results support neurobiological theories positing reduced hippocampal activity under conditions of high stress and arousal. Reduction in MTL activity for successfully encoded stimuli and increased precuneus activity may underlie reduced stimulus-specific encoding and greater gist memory in patients with PTSD, leading to maintenance of the disorder.

Category-selective Background Connectivity in Ventral Visual Cortex

Ventral visual cortex contains specialized regions for particular object categories, but little is known about how these regions interact during object recognition. Here we examine how the face-selective fusiform gyrus (FG) and the scene-selective parahippocampal cortex (PHC) interact with each other and with the rest of the brain during different visual tasks. To assess these interactions, we developed a novel approach for identifying patterns of connectivity associated with specific task sets, independent of stimulus-evoked responses. We tested whether this "background connectivity" between the FG and PHC was modulated when subjects engaged in face and scene processing tasks. In contrast to what would be predicted from biased competition or intrinsic activity accounts, we found that the strength of FG-PHC background connectivity depended on which category was task relevant: connectivity increased when subjects attended to scenes (irrespective of whether a competing face was present) and decreased when subjects attended to faces (irrespective of competing scenes). We further discovered that posterior occipital cortex was correlated selectively with the FG during face tasks and the PHC during scene tasks. These results suggest that category specificity exists not only in which regions respond most strongly but also in how these and other regions interact.

The FMRI BOLD Signal Tracks Electrophysiological Spectral Perturbations, Not Event-related Potentials

Functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) are primary tools of the psychological neurosciences. It is therefore important to understand the relationship between hemodynamic and electrophysiological responses. An early study by Huettel and colleagues found that the coupling of fMRI blood-oxygen-level-dependent signal (BOLD) and subdurally-recorded signal-averaged event-related potentials (ERPs) was not consistent across brain regions. Instead, a growing body of evidence now indicates that hemodynamic changes measured by fMRI reflect non-phase-locked changes in high frequency power rather than the phase-locked ERP. Here, we revisit the data from Huettel and colleagues and measure event-related spectral perturbations (ERSPs) to examine the time course of frequency changes. We found that, unlike the ERP, γ-ERSP power was consistently coupled with the hemodynamic response across three visual cortical regions. Stimulus duration modulated the BOLD signal and the γ-ERSP in the peri-calcarine and fusiform cortices, whereas there was no such modulation of either physiological signal in the lateral temporal-occipital cortex. This finding reconciles the original report with the more recent literature and demonstrates that the ERP and ERSP reflect dissociable aspects of neural activity.

Neural Systems for Guilt from Actions Affecting Self Versus Others

Guilt is a core emotion governing social behavior by promoting compliance with social norms or self-imposed standards. The goal of this study was to contrast guilty responses to actions that affect self versus others, since actions with social consequences are hypothesized to yield greater guilty feelings due to adopting the perspective and subjective emotional experience of others. Sixteen participants were presented with brief hypothetical scenarios in which the participant's actions resulted in harmful consequences to self (guilt-self) or to others (guilt-other) during functional MRI. Participants felt more intense guilt for guilt-other than guilt-self and guilt-neutral scenarios. Guilt scenarios revealed distinct regions of activity correlated with intensity of guilt, social consequences of actions, and the interaction of guilt by social consequence. Guilt intensity was associated with activation of the dorsomedial PFC, superior frontal gyrus, supramarginal gyrus, and anterior inferior frontal gyrus. Guilt accompanied by social consequences was associated with greater activation than without social consequences in the ventromedial and dorsomedial PFC, precuneus, posterior cingulate, and posterior superior temporal sulcus. Finally, the interaction analysis highlighted select regions that were more strongly correlated with guilt intensity as a function of social consequence, including the left anterior inferior frontal gyrus, left ventromedial PFC, and left anterior inferior parietal cortex. Our results suggest these regions intensify guilt where harm to others may incur a greater social cost.

Function Biomedical Informatics Research Network Recommendations for Prospective Multicenter Functional MRI Studies

This report provides practical recommendations for the design and execution of multicenter functional MRI (MC-fMRI) studies based on the collective experience of the Function Biomedical Informatics Research Network (FBIRN). The study was inspired by many requests from the fMRI community to FBIRN group members for advice on how to conduct MC-fMRI studies. The introduction briefly discusses the advantages and complexities of MC-fMRI studies. Prerequisites for MC-fMRI studies are addressed before delving into the practical aspects of carefully and efficiently setting up a MC-fMRI study. Practical multisite aspects include: (i) establishing and verifying scan parameters including scanner types and magnetic fields, (ii) establishing and monitoring of a scanner quality program, (iii) developing task paradigms and scan session documentation, (iv) establishing clinical and scanner training to ensure consistency over time, (v) developing means for uploading, storing, and monitoring of imaging and other data, (vi) the use of a traveling fMRI expert, and (vii) collectively analyzing imaging data and disseminating results. We conclude that when MC-fMRI studies are organized well with careful attention to unification of hardware, software and procedural aspects, the process can be a highly effective means for accessing a desired participant demographics while accelerating scientific discovery. J. Magn. Reson. Imaging 2012;. © 2012 Wiley Periodicals, Inc.

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