Neuroimage

Alerting, orienting, and executive control are widely thought to be relatively independent aspects of attention that are linked to separable brain regions. However, neuroimaging studies have yet to examine evidence for the anatomical separability of these three aspects of attention in the same subjects performing the same task. The attention network test (ANT) examines the effects of cues and targets within a single reaction time task to provide a means of exploring the efficiency of the alerting, orienting, and executive control networks involved in attention. It also provides an opportunity to examine the brain activity of these three networks as they operate in a single integrated task. We used event-related functional magnetic resonance imaging (fMRI) to explore the brain areas involved in the three attention systems targeted by the ANT. The alerting contrast showed strong thalamic involvement and activation of anterior and posterior cortical sites. As expected, the orienting contrast activated parietal sites and frontal eye fields. The executive control network contrast showed activation of the anterior cingulate along with several other brain areas. With some exceptions, activation patterns of these three networks within this single task are consistent with previous fMRI studies that have been studied in separate tasks. Overall, the fMRI results suggest that the functional contrasts within this single task differentially activate three separable anatomical networks related to the components of attention. D

A growing body of evidence suggests that empathy for pain is underpinned by neural structures that are also involved in the direct experience of pain. In order to assess the consistency of this finding, an image-based meta-analysis of nine independent functional magnetic resonance imaging (fMRI) investigations and a coordinate-based meta-analysis of 32 studies that had investigated empathy for pain using fMRI were conducted. The results indicate that a core network consisting of bilateral anterior insular cortex and medial/ anterior cingulate cortex is associated with empathy for pain. Activation in these areas overlaps with activation during directly experienced pain, and we link their involvement to representing global feeling states and the guidance of adaptive behavior for both self-and other-related experiences. Moreover, the image-based analysis demonstrates that depending on the type of experimental paradigm this core network was co-activated with distinct brain regions: While viewing pictures of body parts in painful situations recruited areas underpinning action understanding (inferior parietal/ventral premotor cortices) to a stronger extent, eliciting empathy by means of abstract visual information about the other's affective state more strongly engaged areas associated with inferring and representing mental states of self and other (precuneus, ventral medial prefrontal cortex, superior temporal cortex, and temporo-parietal junction). In addition, only the picture-based paradigms activated somatosensory areas, indicating that previous discrepancies concerning somatosensory activity during empathy for pain might have resulted from differences in experimental paradigms. We conclude that social neuroscience paradigms provide reliable and accurate insights into complex social phenomena such as empathy and that meta-analyses of previous studies are a valuable tool in this endeavor.

Early global deprivation of institutionalized children may result in persistent specific cognitive and behavioral deficits. In order to examine brain dysfunction underlying these deficits, we have applied positron emission tomography using 2-deoxy-2-[ 18 F]fluoro-D-glucose in 10 children (6 males, 4 females, mean age 8.8 years) adopted from Romanian orphanages. Using statistical parametric mapping (SPM), the pattern of brain glucose metabolism in the orphans was compared to the patterns obtained from two control groups: (i) a group of 17 normal adults (9 males, 8 females, mean age 27.6 years) and (ii) a group of 7 children (5 males and 2 females, mean age 10.7 years) with medically refractory focal epilepsy, but normal glucose metabolism pattern in the contralateral hemisphere. Consistent with previous studies of children adopted from Romanian orphanages, neuropsychological assessment of Romanian orphans in the present study showed mild neurocognitive impairment, impulsivity, and attention and social deficits. Comparing the normalized glucose metabolic rates to those of normal adults, the Romanian orphans showed significantly decreased metabolism bilaterally in the orbital frontal gyrus, the infralimbic prefrontal cortex, the medial temporal structures (amygdala and head of hippocampus), the lateral temporal cortex, and the brain stem. These findings were confirmed using a region-of-interest approach. SPM analysis showed significantly decreased glucose metabolism in the same brain regions comparing the orphans to the nonepileptic hemisphere of the childhood epilepsy controls. Dysfunction of these brain regions may result from the stress of early global deprivation and may be involved in the long-term cognitive and behavioral deficits displayed by some Romanian orphans.

The techniques available for the interrogation and analysis of neuroimaging data have a large influence in determining the flexibility, sensitivity, and scope of neuroimaging experiments. The development of such methodologies has allowed investigators to address scientific questions that could not previously be answered and, as such, has become an important research area in its own right. In this paper, we present a review of the research carried out by the Analysis Group at the Oxford Centre for Functional MRI of the Brain (FMRIB). This research has focussed on the development of new methodologies for the analysis of both structural and functional magnetic resonance imaging data. The majority of the research laid out in this paper has been implemented as freely available software tools within FMRIB's Software Library (FSL).

Theory of Mind (ToM), the ability to attribute mental states to others, and empathy, the ability to infer emotional experiences, are important processes in social cognition. Brain imaging studies in healthy subjects have described a brain system involving medial prefrontal cortex, superior temporal sulcus and temporal pole in ToM processing. Studies investigating networks associated with empathic responding also suggest involvement of temporal and frontal lobe regions. In this fMRI study, we used a cartoon task derived from [Sarfati, Y., Hardy-Bayle, M.C., Besche, C., Widlocher, D. 1997. Attribution of intentions to others in people with schizophrenia: a non-verbal exploration with comic strips. Schizophrenia Research 25,[199][200][201][202][203][204][205][206][207][208][209] with both ToM and empathy stimuli in order to allow comparison of brain activations in these two processes. Results of 13 right-handed, healthy, male volunteers were included. Functional images were acquired using a 1.5 T Phillips Gyroscan. Our results confirmed that ToM and empathy stimuli are associated with overlapping but distinct neuronal networks. Common areas of activation included the medial prefrontal cortex, temporoparietal junction and temporal poles. Compared to the empathy condition, ToM stimuli revealed increased activations in lateral orbitofrontal cortex, middle frontal gyrus, cuneus and superior temporal gyrus. Empathy, on the other hand, was associated with enhanced activations of paracingulate, anterior and posterior cingulate and amygdala. We therefore suggest that ToM and empathy both rely on networks associated with making inferences about mental states of others. However, empathic responding requires the additional recruitment of networks involved in emotional processing. These results have implications for our understanding of disorders characterized by impairments of social cognition, such as autism and psychopathy. D

Borderline personality disorder (BPD) is a severe psychiatric condition of undetermined brain underpinnings, which involves profound emotion regulation deficits and interpersonal impairment. To elucidate biopsychological markers of the disorder, we performed two studies: i.) assessing empathy and social cognition and ii.) measuring the psychophysical properties and functional brain correlates of empathic functioning in a total of fifty-one affected patients and 50 age-and gender-matched controls. In the behavioral study we applied the Multifaceted Empathy Test (MET), a new, ecologically valid measure to assess cognitive (i.e., social cognition) and emotional (i.e., empathic concern) empathy to a subset of participants. In the second study, functional Magnetic Resonance Imaging and skin conductance measurements were performed while participants took a scanner-adapted version of the MET. Patients with BPD showed impairments in cognitive and emotional empathy. Brain responses during cognitive empathy were significantly reduced in patients compared to controls in the left superior temporal sulcus and gyrus (STS/STG), where this reduction was associated with levels of intrusive symptomatology in the BPD group. During emotional empathy, patients with BPD exhibited greater brain activity than controls in the right middle insular cortex, a response that was associated with skin conductance responses in the patients. Results indicate that altered functioning of the STS/STG and insula represents pathophysiological mediators for reduced empathy in BPD, with an important role for intrusive symptomatology and levels of arousal. The findings thus support a conceptualization of BPD as involving deficits in both inferring others' mental states and being emotionally attuned to another person.

The hypothalamic-pituitary-adrenal (HPA) axis is the major endocrine stress axis of the human organism. Cortisol, the final hormone of this axis, affects metabolic, cardiovascular and central nervous systems both acutely and chronically. Recent advances in neuroimaging techniques have led to the investigation of regulatory networks and mechanisms of cortisol regulation in the central nervous system in human populations. In the following review, results from human and animal studies are being presented that investigate the specific role of hippocampus (HC), amygdala (AG), prefrontal cortex (PFC), and brainstem nuclei in cortisol regulation in response to stress. In general, the types of stressors need to be distinguished when discussing the contributions of these structures in regulating the HPA axis. We propose a basic framework on how these structures communicate as a network to regulate cortisol secretion in response to psychological stress. Furthermore, we review critical studies that have substantially contributed to the literature. Possible future research avenues in the field of neuroimaging of cortisol regulation are discussed. In combination with investigations on genetic and environmental factors that influence the development of the HPA axis, this emerging new research will eventually allow the formulation of a more comprehensive framework of functional neuroanatomy of cortisol regulation.

Little is known about the effects of successful psychotherapy on brain function in subjects with anxiety disorders. The present study aimed to identify changes in brain activation following cognitive-behavioral therapy (CBT) in subjects suffering from specific phobia. Using functional magnetic resonance imaging (fMRI), brain activation to spider videos was measured in 28 spider phobic and 14 healthy control subjects. Phobics were randomly assigned to a therapy-group (TG) and a waiting-list control group (WG). Both groups of phobics were scanned twice. Between scanning sessions, CBT was given to the TG. Before therapy, brain activation did not differ between both groups of phobics. As compared to control subjects, phobics showed greater responses to spider vs. control videos in the insula and anterior cingulate cortex (ACC). CBT strongly reduced phobic symptoms in the TG while the WG remained behaviorally unchanged. In the second scanning session, a significant reduction of hyperactivity in the insula and ACC was found in the TG compared to the WG. These results propose that increased activation in the insula and ACC is associated with specific phobia, whereas an attenuation of these brain responses correlates with successful therapeutic intervention. D

Using two languages on an everyday basis appears to have a positive effect on general-purpose executive control in bilinguals. However, the neural correlates of this effect remain poorly understood. To investigate the brain bases of the bilingual advantage in executive control, we tested 21 Spanish monolinguals and 19 Spanish-Catalan early bilinguals in a non-verbal task-switching paradigm. As expected based on previous experiments on non-verbal task switching, we found activation in the right inferior frontal cortex and the anterior cingulate of monolingual participants. While bilingual participants showed a reduced switching cost, they activated the left inferior frontal cortex and the left striatum, a pattern of activation consistent with networks thought to underlie language control. Overall, these results support the hypothesis that bilinguals' early training in switching back and forth between their languages leads to the recruitment of brain regions involved in language control when performing non-linguistic cognitive tasks.

Numerous studies concerned with cerebral structures underlying word reading have been published during the last decade. A few controversies, however, together with methodological or theoretical discrepancies between laboratories, still contribute to blurring the overall view of advances effected in neuroimaging. Carried out within the dual route of reading framework, the aim of this metanalysis was to provide an objective picture of these advances. To achieve this, we used an automated analysis method based on the inventory of activation peaks issued from word or pseudoword reading contrasts of 35 published neuroimaging studies. A first result of this metanalysis was that no cluster of activations has been found more recruited by word than pseudoword reading, implying that the first steps of word access may be common to word and word-like stimuli and would take place within a left occipitotemporal region (previously referred to as the Visual Word Form Area-VWFA) situated in the ventral route, at the junction between inferior temporal and fusiform gyri. The results also indicated the existence of brain regions predominantly involved in one of the two routes to access word. The graphophonological conversion seems indeed to rely on left lateralized brain structures such as superior temporal areas, supramarginal gyrus, and the opercular part of the inferior frontal gyrus, these last two regions reflecting a greater load in working memory during such an access. The lexicosemantic route is thought to arise from the coactivation of the VWFA and semantic areas. These semantic areas would encompass a basal inferior temporal area, the posterior part of the middle temporal gyrus, and the triangular part of inferior frontal gyrus. These results confirm the suitability of the dual route framework to account for activations observed in nonpathological subjects while they read.

This meta-analysis explores the role of the mirror and mentalizing systems in the understanding of other people's action goals. Based on over 200 fMRI studies, this analysis demonstrates that the mirror systemconsisting of the anterior intraparietal sulcus and the premotor cortexis engaged when one perceives articulated motions of body parts irrespective of their sensory (visual or auditory) or verbal format as well as when the perceiver executes them. This confirms the matching role of the mirror system in understanding biological action. Observation of whole-body motions and gaze engage the posterior superior temporal sulcus and most likely reflects an orientation response in line with the action or attention of the observed actor. In contrast, the mentalizing systemconsisting of the temporo-parietal junction, the medial prefrontal cortex and the precuneusis activated when behavior that enables inferences to be made about goals, beliefs or moral issues is presented in abstract terms (e.g., verbal stories or geometric shapes) and there is no perceivable biological motion of body parts. A striking overlap of brain activity at the temporo-parietal junction between social inferences and other, non-social observations (e.g., Posner's cuing task) suggests that this area computes the orientation or direction of the behavior in order to predict its likely end-state (or goal). No conclusions are drawn about the specific functionality of the precuneus and the medial prefrontal cortex. Because the mirror and mentalizing systems are rarely concurrently active, it appears that neither system subserves the other. Rather, they are complementary. There seems, however, to be a transition from the mirror to the mentalizing system even when body-part motions are observed by perceivers who are consciously deliberating about the goals of others and their behavioral executions, such as when perceived body motions are contextually inconsistent, implausible or pretended.

Alexithymic individuals have difficulty in recognizing and describing emotions in themselves. We investigated the neuronal basis of mentalizing in alexithymia to determine whether there is a common neuronal substrate associated with knowing the mental states of the self and others. Individuals high in alexithymia (n = 16) and low in alexithymia (n = 14) were selected from a pool of 310 college students using a combination of the Toronto Alexithymia Scale (TAS-20) and the Structured Interview version of the Beth Israel Questionnaire (SIBIQ). We compared the two groups on psychological measures, including ratings of mentalizing and the Interpersonal Reactivity Index (IRI), and regional brain activation using functional magnetic resonance imaging (fMRI) during a mentalizing animation task. The results for both groups showed activation in regions associated with mentalizing: medial prefrontal cortices (MPFC), temporo-parietal junctions (TPJ), and the temporal pole (TP). Alexithymics had lower mentalizing and IRI perspective-taking scores and less activation in the right MPFC. Activity in the MPFC was positively correlated with the mentalizing score and the IRI perspective-taking score. Although there were no group differences in cerebral activity in the TPJ and the TP, the activity in the right TP had a positive correlation with mentalizing and IRI personal distress scores. These results suggest that alexithymic individuals have an impairment in mentalizing associated with an inability to take the perspective of others. Thus, the skills involved in comprehending the self and others are inter-related and play an important role in emotion regulation. D

Several neuroimaging studies have reported dhypofrontalityT in depressed patients performing a cognitive challenge compared to control subjects. Hypofrontality in depression is likely associated with an impaired behavioral performance. It is unclear whether this impaired performance is the consequence or the cause of hypofrontality. Consequently, we proposed to compare the cerebral activity of depressed patients and healthy subjects while controlling for the level of performance. Ten individuals meeting DSM-IV criteria for Major Depression and 10 healthy controls were tested with a verbal version of the n-back task during fMRI scanning. The working memory load was manipulated across the experiment (1,2,3-back) to increase the cognitive demands. fMRI data were acquired on a 1.5-T GE scanner and analyzed using SPM99 software. We did not find any difference between groups in both performance and reaction times for each level of complexity of the n-back task. Depressed patients and control subjects showed bilateral activation of the lateral prefrontal cortex, anterior cingulate and parietal cortex. Activation of these regions was modulated by the complexity of the task. Within this n-back neural network, depressed patients showed greater activation of the lateral prefrontal cortex and the anterior cingulate compared to healthy subjects. This study provides evidence that depressed patients need greater activation within the same neural network to maintain a similar level of performance as controls during a working memory task. Our findings suggest that depression may impair the cognitive capacity of depressed patients by recruiting more brain resources than controls during cognitive control. D

Recent debates about the conventional traditional threshold used in the fields of neuroscience and psychology, namely P < 0.05, have spurred researchers to consider alternative ways to analyze fMRI data. A group of methodologists and statisticians have considered Bayesian inference as a candidate methodology. However, few previous studies have attempted to provide end users of fMRI analysis tools, such as SPM 12, with practical guidelines about how to conduct Bayesian inference. In the present study, we aim to demonstrate how to utilize Bayesian inference, Bayesian second-level inference in particular, implemented in SPM 12 by analyzing fMRI data available to public via NeuroVault. In addition, to help end users understand how Bayesian inference actually works in SPM 12, we examine outcomes from Bayesian second-level inference implemented in SPM 12 by comparing them with those from classical second-level inference. Finally, we provide practical guidelines about how to set the parameters for Bayesian inference and how to interpret the results, such as Bayes factors, from the inference. We also discuss the practical and philosophical benefits of Bayesian inference and directions for future research.

Evidence exists that the observation of actions activates the same cortical motor areas that are involved in the performance of the observed actions. The neural substrate for this is the mirror neuron system. We harness this neuronal system and its ability to re-enact stored motor representations as a means for rehabilitating motor control.

The objective of this study was to delineate a common functional network that underlies autobiographical, episodic, and semantic memory retrieval. We conducted an event-related fMRI study in which we utilized the same pictorial stimuli, but manipulated retrieval demands to extract autobiographical, episodic, or semantic memories. To assess this common network, we first examined the functional connectivity of regions identified by a previous analysis of task-related activity that were active across all three tasks. Three of these regions (left hippocampus, left lingual gyrus, and right caudate nucleus) appeared to share a common pattern of connectivity. This was confirmed in a subsequent functional connectivity analysis using these three regions as seeds. The results of this analysis showed that there was a pattern of functional connectivity that characterized all three seeds and that was common across the three retrieval conditions. Activity in inferior frontal and middle temporal cortex bilaterally, left temporoparietal junction, and anterior and posterior cingulate gyri was positively correlated with the seeds, whereas activity in posterior occipitotemporo-parietal regions was negatively correlated. These findings support the idea that a common neural network underlies the retrieval of declarative memories regardless of memory content. This proposed network consists of increased activity in regions that represent internal processes of memory retrieval and decreased activity in regions that mediate attention to external stimuli.

The current experiment was designed to investigate the nature of cognitive control in within-and between-language switching in bilingual participants. To examine the neural substrate of language switching we used functional magnetic resonance imaging (fMRI) as subjects named pictures in one language only or switched between languages. Participants were also asked to name (only in English) a separate set of pictures as either the actions or the objects depicted or to switch between these two types of responses on each subsequent picture. Picture naming compared to rest revealed activation in the dorsolateral prefrontal cortex, which extended down into Broca's area in the left hemisphere. There were no differences in the activation pattern for each language. English and Spanish both activated overlapping areas of the brain. Similarly, there was no difference in activation for naming actions or objects in English. However, there was increased intensity of activation in the dorsolateral prefrontal cortex for switching between languages relative to no-switching, an effect which was not observed for naming of actions or objects in English. We suggest that the dorsolateral prefrontal cortex serves to attenuate interference that results from having to actively enhance and suppress two languages in alternation. These results are consistent with the view that switching between languages involves increased general executive processing. Finally, our results are consistent with the view that different languages are represented in overlapping areas of the brain in early bilinguals.

Alerting, orienting, and executive control are widely thought to be relatively independent aspects of attention that are linked to separable brain regions. However, neuroimaging studies have yet to examine evidence for the anatomical separability of these three aspects of attention in the same subjects performing the same task. The attention network test (ANT) examines the effects of cues and targets within a single reaction time task to provide a means of exploring the efficiency of the alerting, orienting, and executive control networks involved in attention. It also provides an opportunity to examine the brain activity of these three networks as they operate in a single integrated task. We used event-related functional magnetic resonance imaging (fMRI) to explore the brain areas involved in the three attention systems targeted by the ANT. The alerting contrast showed strong thalamic involvement and activation of anterior and posterior cortical sites. As expected, the orienting contrast activated parietal sites and frontal eye fields. The executive control network contrast showed activation of the anterior cingulate along with several other brain areas. With some exceptions, activation patterns of these three networks within this single task are consistent with previous fMRI studies that have been studied in separate tasks. Overall, the fMRI results suggest that the functional contrasts within this single task differentially activate three separable anatomical networks related to the components of attention. D

The present study used magneto-encephalography (MEG) to determine the neural correlates of the bilingual advantage previously reported for behavioral measures in conflict tasks. Bilingual Cantonese–English, bilingual French–English, and monolingual English speakers, ...

Theoretical models of hypnosis have emphasized the importance of attentional processes in accounting for hypnotic phenomena but their exact nature and brain substrates remain unresolved. Individuals vary in their susceptibility to hypnosis, a variability often attributed to differences in attentional functioning such as greater ability to filter irrelevant information and inhibit prepotent responses. However, behavioral studies of attentional performance outside the hypnotic state have provided conflicting results. We used fMRI to investigate the recruitment of attentional networks during a modified flanker task in High and Low hypnotizable participants. The task was performed in a normal (no hypnotized) state. While behavioral performance did not reliably differ between groups, components of the fronto-parietal executive network implicated in monitoring (anterior cingulate cortex; ACC), adjustment (lateral prefrontal cortex; latPFC), and implementation of attentional control (intraparietal sulcus; IPS) were differently activated depending on the hypnotizability of the subjects: the right inferior frontal gyrus (rIFG) was more recruited, whereas IPS and ACC were less recruited by High susceptible individuals compared to Low. Our results demonstrate that susceptibility to hypnosis is associated with particular executive control capabilities allowing efficient attentional focusing, and point to specific neural substrates in right prefrontal cortex. Significance statement: We demonstrated that outside hypnosis, low hypnotizable subjects recruited more parietal cortex and anterior cingulate regions during selective attention conditions suggesting a better detection and implementation of conflict. However, outside hypnosis the right inferior frontal gyrus (rIFG) was more recruited by highly hypnotizable subjects during selective attention conditions suggesting a better control of conflict. Furthermore, in highly hypnotizable subjects this region was more connected to the default mode network suggesting a tight dialogue between internally and externally driven processes that may permit higher flexibility in attention and underlie a greater ability to dissociate.

Intrinsic and phasic alertness are the most basic aspects of attention intensity probably constituting the basis for the more complex and capacity-demanding aspects of attention selectivity. Intrinsic alertness represents the cognitive control of wakefulness and arousal and is typically assessed by simple reaction time tasks without a preceding warning stimulus. Phasic alertness, in contrast, is called for in reaction time tasks in which a warning stimulus precedes the target, and it represents the ability to increase response readiness subsequent to external cueing. We report PET and fMRI data from both the literature and our own experiments to delineate the cortical and subcortical networks subserving alertness, sustained attention (as another aspect of attention intensity), and spatial orienting of attention. Irrespective of stimulus modality, there seems to exist a mostly right-hemispheric frontal, parietal, thalamic, and brain-stem network which is coactivated by alerting and orienting attentional demands. These findings corroborate both the hypothesis of a frontal modulation of brain-stem activation probably via the reticular nucleus of the thalamus and of a coactivation of the posterior attention system involved in spatial orienting by the anterior alerting network. Under conditions of phasic alertness there are additional activations of left-hemisphere frontal and parietal structures which are interpreted as basal aspects of attention selectivity rather than additional features of alerting.

Empathy allows us to simulate others' affective and cognitive mental states internally, and it has been proposed that the mirroring or motor representation systems play a key role in such simulation. As emotions are related to important adaptive events linked with benefit or danger, simulating others' emotional states might constitute of a special case of empathy. In this functional magnetic resonance imaging (fMRI) study we tested if emotional versus cognitive empathy would facilitate the recruitment of brain networks involved in motor representation and imitation in healthy volunteers. Participants were presented with photographs depicting people in neutral everyday situations (cognitive empathy blocks), or suffering serious threat or harm (emotional empathy blocks). Participants were instructed to empathize with specified persons depicted in the scenes. Emotional versus cognitive empathy resulted in increased activity in limbic areas involved in emotion processing (thalamus), and also in cortical areas involved in face (fusiform gyrus) and body perception, as well as in networks associated with mirroring of others' actions (inferior parietal lobule). When brain activation resulting from viewing the scenes was controlled, emotional empathy still engaged the mirror neuron system (premotor cortex) more than cognitive empathy. Further, thalamus and primary somatosensory and motor cortices showed increased functional coupling during emotional versus cognitive empathy. The results suggest that emotional empathy is special. Emotional empathy facilitates somatic, sensory, and motor representation of other peoples' mental states, and results in more vigorous mirroring of the observed mental and bodily states than cognitive empathy.

Conjunction analysis methods were used in functional magnetic resonance imaging to investigate brain regions commonly activated in subjects performing different versions of go/no-go and stop tasks, differing in probability of inhibitory signals and/or contrast conditions. Generic brain activation maps highlighted brain regions commonly activated in (a) two different go/no-go task versions, (b) three different stop task versions, and (c) all 5 inhibition task versions. Comparison between the generic activation maps of stop and go/no-go task versions revealed inhibitory mechanisms specific to go/no-go or stop task performance in 15 healthy, right-handed, male adults. In the go/no-go task a motor response had to be selectively executed or inhibited in either 50% or 30% of trials. In the stop task, the motor response to a gostimulus had to be retracted on either 50 or 30% of trials, indicated by a stop signal, shortly (250 ms) following the go-stimulus. The shared "inhibitory" neurocognitive network by all inhibition tasks comprised mesial, medial, and inferior frontal and parietal cortices. Generic activation of the go/no-go task versions identified bilateral, but more predominantly left hemispheric mesial, medial, and inferior frontal and parietal cortices. Common activation to all stop task versions was in predominantly right hemispheric anterior cingulate, supplementary motor area, inferior prefrontal, and parietal cortices. On direct comparison between generic stop and go/no-go activation maps increased BOLD signal was observed in left hemispheric dorsolateral prefrontal, medial, and parietal cortices during the go/no-go task, presumably reflecting a left frontoparietal specialization for response selection.

Neuroimaging and neuropsychological studies have implicated left inferior prefrontal cortex (LIPC) in both semantic and phonological processing. In this study, functional magnetic resonance imaging was used to examine whether separate LIPC regions participate in each of these types of processing. Performance of a semantic decision task resulted in extensive LIPC activation compared to a perceptual control task. Phonological processing of words and pseudowords in a syllable-counting task resulted in activation of the dorsal aspect of the left inferior frontal gyrus near the inferior frontal sulcus (BA 44/45) compared to a perceptual control task, with greater activation for nonwords compared to words. In a direct comparison of semantic and phonological tasks, semantic processing preferentially activated the ventral aspect of the left inferior frontal gyrus (BA 47/45). A review of the literature demonstrated a similar distinction between left prefrontal regions involved in semantic processing and phonological/lexical processing. The results suggest that a distinct region in the left inferior frontal cortex is involved in semantic processing, whereas other regions may subserve phonological processes engaged during both semantic and phonological tasks. 1999

Neuroimaging studies investigating emotion have commonly used two different visual stimulus formats, facial expressions of emotion or emotionally evocative scenes. However, it remains an important unanswered question whether or not these different stimulus formats entail the same processes. Facial expressions of emotion may elicit more emotion recognition/perception, and evocative pictures may elicit more direct experience of emotion. In spite of these differences, common areas of activation have been reported across different studies, but little work has investigated activations in response to the two stimulus formats in the same subjects. In this fMRI study, we compared BOLD activation patterns to facial expression of emotions and to complex emotional pictures from the International Affective Picture System (IAPS) to determine if these stimuli would activate similar or distinct brain regions. Healthy volunteers passively viewed blocks of expressive faces and IAPS pictures balanced for specific emotion (happy, sad, anger, fear, neutral), interleaved with blocks of fixation. Eye movement, reaction times, and off-line subjective ratings including discrete emotion, valence, and arousal were also recorded. Both faces and IAPS pictures activated similar structures, including the amygdala, posterior hippocampus, ventromedial prefrontal cortex, and visual cortex. In addition, expressive faces uniquely activated the superior temporal gyrus, insula, and anterior cingulate more than IAPS pictures, despite the faces being less arousing. For the most part, these regions were activated in response to all specific emotions; however, some regions responded only to a subset. D

We aimed to investigate the neural substrates associated with evaluative process of moral emotions. Using functional magnetic resonance imaging (fMRI), we examined the similarities and differences between evaluative process of guilt and that of embarrassment at the neural basis level. Study of the neural basis of judgments of moral emotions might contribute to a better understanding of the amoral behavior observed in neurological and psychiatric disorders. Nineteen healthy volunteers were studied. The participants read sentences carrying neutral, guilty, or embarrassing contents during the scans. Both guilt and embarrassment conditions commonly activated the medial prefrontal cortex (MPFC), left posterior superior temporal sulcus (STS), and visual cortex. Compared to guilt condition, embarrassment condition produced greater activation in the right temporal cortex (anterior), bilateral hippocampus, and visual cortex. Most of these regions have been implicated in the neural substrate of social cognition or Theory of Mind (ToM). Our results support the idea that both are self-conscious emotions, which are social emotions requiring the ability to represent the mental states of others. At the same time, our functional fMRI data are in favor of the notion that evaluative process of embarrassment might be a more complex process than that of guilt. D

There is ongoing debate about how semantic information is acquired, whether this occurs independently of episodic memory, and what role, if any, brain areas such as hippocampus are required to play. We used auditory stimuli and functional MRI (fMRI) to assess brain activations associated with the incidental acquisition of new and true facts about the world of the sort we are exposed to day to day. A control task was included where subjects heard sentences that described novel scenarios involving unfamiliar people, but these did not convey general knowledge. The incidental encoding task was identical for two stimulus types; both shared the same episodic experience (lying in the brain scanner) and conveyed complex information. Despite this, and considering only those stimuli successfully encoded, compared to a baseline task, a more extensive network of brain regions was found to be associated with exposure to new facts including the hippocampus. Direct comparison between the two stimulus types revealed greater activity in dorsal, ventrolateral and dorsomedial prefrontal cortex, medial dorsal nucleus of the thalamus, and temporal cortex for fact stimuli. The findings suggest that successful encoding is not invariably associated with activation of one particular brain network. Rather, activation patterns may depend on the type of materials being acquired, and the different processes they engender when subjects encode. Qualitatively, from postscan debriefing sessions, it emerged that the factual information was found to be potentially more useful. We suggest that current or prospective utility of incoming information may be one factor that influences the processes engaged during encoding and the concomitant neuronal responses. D

Reward prediction error (RPE) Feedback-related negativity (FRN) Dorsal anterior cingulate cortex (dACC) Simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) Surprise Dynamic causal modeling (DCM) Probabilistic reversal learning Changes in response contingencies require adjusting ones assumptions about outcomes of behaviors. Such adaptation processes are driven by reward prediction error (RPE) signals which reflect the inadequacy of expectations. Signals resembling RPEs are known to be encoded by mesencephalic dopamine neurons projecting to the striatum and frontal regions. Although regions that process RPEs, such as the dorsal anterior cingulate cortex (dACC), have been identified, only indirect evidence links timing and network organization of RPE processing in humans. In electroencephalography (EEG), which is well known for its high temporal resolution, the feedbackrelated negativity (FRN) has been suggested to reflect RPE processing. Recent studies, however, suggested that the FRN might reflect surprise, which would correspond to the absolute, rather than the signed RPE signals. Furthermore, the localization of the FRN remains a matter of debate. In this simultaneous EEG-functional magnetic resonance imaging (fMRI) study, we localized the FRN directly using the superior spatial resolution of fMRI without relying on any spatial constraint or other assumption. Using two different single-trial approaches, we consistently found a cluster within the dACC. One analysis revealed additional activations of the salience network. Furthermore, we evaluated the effect of signed RPEs and surprise signals on the FRN amplitude. We considered that both signals are usually correlated and found that only surprise signals modulate the FRN amplitude. Last, we explored the pathway of RPE signals using dynamic causal modeling (DCM). We found that the surprise signals are directly projected to the source region of the FRN. This finding contradicts earlier theories about the network organization of the FRN, but is in line with a recent theory stating that dopamine neurons also encode surprise-like saliency signals. Our findings crucially advance the understanding of the FRN. We found compelling evidence that the FRN originates from the dACC. Furthermore, we clarified the functional role of the FRN, and determined the role of the dACC within the RPE network. These findings should enable us to study the processing of surprise and adjustment signals in the dACC in healthy and also in psychiatric patients.

The mirror neuron system (MNS) has been proposed to play an important role in social cognition by providing a neural mechanism by which others' actions, intentions, and emotions can be understood. Here functional magnetic resonance imaging was used to directly examine the relationship between MNS activity and two distinct indicators of social functioning in typically-developing children (aged 10.1 years ± 7 months): empathy and interpersonal competence. Reliable activity in pars opercularis, the frontal component of the MNS, was elicited by observation and imitation of emotional expressions. Importantly, activity in this region (as well as in the anterior insula and amygdala) was significantly and positively correlated with established behavioral measures indexing children's empathic behavior (during both imitation and observation) and interpersonal skills (during imitation only). These findings suggest that simulation mechanisms and the MNS may indeed be relevant to social functioning in everyday life during typical human development.

Intersubject variability and subtle differences in experimental design can lead to variable results in studies of cognitive processes such as reading. To accurately identify the neural processes associated with cognition and sensorimotor processing, meta-analytic methods capable of identifying areas of consistent activation among studies are useful. This paper describes a novel approach for combining published neuroimaging results from multiple studies, designed to maximize the quantification of interstudy concordance while minimizing the subjective aspects of meta-analysis. In this method, a localization probability distribution was modeled for each activation focus obtained from 11 PET studies of reading single words aloud, and the union of these distributions was taken to yield an activation likelihood estimate map for the brain. Significance was assessed via permutation analysis of randomly generated sets of foci. Regions of significant concordance were identified in bilateral motor and superior temporal cortices, pre-SMA, left fusiform gyrus, and the cerebellum. These meta-analytic results were validated by comparison with new fMRI data on aloud word reading in normal adult subjects. Excellent correspondence between the two statistical maps was observed, with fMRI maxima lying close to all meta-analysis peaks and statistical values at the peaks identified by the two techniques correlating strongly. This close correspondence between PET meta-analysis and fMRI results also demonstrates the validity of using fMRI for the study of language tasks involving overt speech responses. Advantages of this automated meta-analysis technique include quantification of the level of concordance at all brain locations and the provision for use of a threshold for statistical significance of concordance.

How the brain deals with more than one language and whether we need different or extra brain language subnetworks to support more than one language remain unanswered questions. Here, we investigate structural brain network differences between early bilinguals and monolinguals. Using diffusion-weighted MRI (DW-MRI) tractography techniques and a network-based statistic (NBS) procedure, we found two structural subnetworks more connected by white matter (WM) tracts in bilinguals than in monolinguals; confirming WM brain plasticity in bilinguals. One of these sub-networks comprises left frontal and parietal/temporal regions, while the other comprises left occipital and parietal/temporal regions and also the right superior frontal gyrus. Most of these regions have been related to language processing and monitoring; suggesting that bilinguals develop specialized language sub-networks to deal with the two languages. Additionally, a complex network analysis showed that these sub-networks are more graph-efficient in bilinguals than monolinguals and this increase seems to be at the expense of a whole-network graph-efficiency decrease.

Subjects participated in perceptual and imagery tasks while their brains were scanned using positron emission tomography. In the perceptual conditions, subjects judged whether names were appropriate for pictures. In one condition, the objects were pictured from canonical perspectives and could be recognized at first glance; in the other, the objects were pictured from noncanonical perspectives and were not immediately recognizable. In this second condition, we assume that top-down processing is used to evaluate the names. In the imagery conditions, subjects saw a grid with a single X mark; a lowercase letter was presented before the grid. In the baseline condition, they simply responded when they saw the stimulus, whereas in the imagery condition they visualized the corresponding block letter in the grid and decided whether it would have covered the X if it were physically present. Fourteen areas were activated in common by both tasks, only 1 of which may not be involved in visual processing (the precentral gyrus); in addition, 2 were activated in perception but not imagery, and 5 were activated in imagery but not perception. Thus, two-thirds of the activated areas were activated in common. 1997

Most of us use numbers daily for counting, estimating quantities or formal mathematics, yet despite their importance our understanding of the brain correlates of these processes is still evolving. A neurofunctional model of mental arithmetic, proposed more than a decade ago, stimulated a substantial body of research in this area. Using quantitative meta-analyses of fMRI studies we identified brain regions concordant among studies that used number and calculation tasks. These tasks elicited activity in a set of common regions such as the inferior parietal lobule; however, the regions in which they differed were most notable, such as distinct areas of prefrontal cortices for specific arithmetic operations. Given the current knowledge, we propose an updated topographical brain atlas of mental arithmetic with improved interpretative power.

Social anxiety disorder patients suffer from excessive anxious responses in social interaction leading to avoidance behavior and social impairment. Although the amygdala has a central role in perception and processing of threatening cues, little is known about the involved networks and corresponding dysfunctions in social anxiety. Therefore, this study aims to investigate the functional connectivity network of the amygdala in patients with social anxiety disorder and to identify regions that might influence amygdalar reactivity via modulatory pathways. Ten patients with anxiety disorders (social and/or panic) and 27 healthy controls underwent a facial emotion processing task as well as 6-min functional MRI at resting state. Individual voxel-wise functional connectivity maps were calculated using the amygdala as seed region. Group comparisons were done by random-effects analysis in SPM. Patients exhibited an amygdala hyperactivation during the emotional task and decreased functional ...

Cannabis abuse is related to impairments in a broad range of cognitive functions. However, studies on cannabis abuse in relation to brain structure are sparse and results are inconsistent, probably due to differences in imaging methodology, severity of cannabis abuse, and use of other substances. The goal of the current MRI study was to investigate brain morphology related to current and lifetime severity of cannabis use and dependence in heavy cannabis users without intensive use of other illicit drugs. Voxel-based morphometry was used to assess differences in regional grey and white matter volume between 33 heavy cannabis users and 42 matched controls. Within heavy cannabis users, grey and white matter volume was correlated with measures of cannabis use and dependence. Analyses were focused a priori on the orbitofrontal cortex, anterior cingulate cortex, striatum, amygdala, hippocampus, and cerebellum, regions implicated in substance dependence and/or with high cannabinoid receptor-1 concentrations. Regional grey matter volume in the anterior cerebellum was larger in heavy cannabis users. Within the group of heavy cannabis users, grey matter volume in the amygdala and hippocampus correlated negatively with the amount of cannabis use or dependence. No associations were found between white matter volume and measures of cannabis use or dependence. These findings indicate that associations between heavy cannabis use and altered brain structure are complex. Differential patterns of structural changes for various cannabis use levels imply that alterations in brain structure are associated with specific characteristics of cannabis use and dependence.

Cognitive abilities such as working memory (WM) capacity decrease with age. To determine the neurophysiological correlates of age-related reduction in working memory capacity, we studied 10 young subjects (<35 years of age; mean age = 29) and twelve older subjects (>55 years of age; mean age = 59) with whole brain blood oxygenation-level dependent (BOLD) fMRI on a 1.5 T GE MR scanner using a SPIRAL FLASH pulse sequence (TE = 24 ms, TR = 56 ms, FA = 60 • , voxel dimensions = 3.75 mm 3 ). Subjects performed a modified version of the "n" back working memory task at different levels of increasing working memory load (1-Back, 2-Back and 3-Back). Older subjects performed as well as the younger subjects at 1-Back (p = 0.4), but performed worse than the younger subjects at 2-Back (p < 0.01) and 3-Back (p = 0.06). Older subjects had significantly longer reaction time (RT) than younger subjects (p < 0.04) at all levels of task difficulty. Image analysis using SPM 99 revealed a similar distribution of cortical activity between younger and older subjects at all task levels. However, an analysis of variance revealed a significant group × task interaction in the prefrontal cortex bilaterally; within working memory capacity, as in 1-Back when the older subjects performed as well as the younger subjects, they showed greater prefrontal cortical (BA 9) activity bilaterally. At higher working memory loads, however, when they performed worse then the younger subjects, the older subjects showed relatively reduced activity in these prefrontal regions. These data suggest that, within capacity, compensatory mechanisms such as additional prefrontal cortical activity are called upon to maintain proficiency in task performance. As cognitive demand increases, however, they are pushed past a threshold beyond which physiological compensation cannot be made and, a decline in performance occurs.

In this fMRI study, we investigated the convergence of underlying neural networks in thinking about a scenario involving one's own intentional action and its consequences and setting up and holding in mind an intention to act. A factorial design was employed comprising two factors: i. Causality (intentional or physical events) and ii. Prospective Memory (present or absent). In each condition, subjects answered questions about various hypothetical scenarios, which related either to the link between the subject's own intentions and consequential actions (Intentional Causality) or to the link between a natural, physical event and its consequences (Physical Causality). A prospective memory task was embedded in half the blocks. In this task, subjects were required to keep in mind an intention (to press a key on seeing a red stimulus background) whilst carrying out the ongoing Causality task. Answering questions about intentional causality versus physical causality activated a network of regions that have traditionally been associated with Theory of Mind, including the medial prefrontal cortex (mPFC), the superior temporal sulcus and the temporal poles bilaterally. In addition, the precuneus bordering with posterior cingulate cortex, an area involved in self-awareness and self-related processing, was activated more when thinking about intentional causality. In the prospective memory task, activations were found in the right parietal cortex, frontopolar cortex (BA 10) and precuneus. Different subregions within the precuneus/posterior cingulate cortex were activated in both main effects of intentional causality and prospective memory. Therefore, the precuneus/posterior cingulate cortex subserves separately thinking about one's own intentions and consequent actions and bearing in mind an intention to make an action. Previous studies have shown that prospective memory, requiring the formation of an intention and the execution of a corresponding action, is associated with decreased activation in the dorsal mPFC, close to the region activated in Theory of Mind tasks. Here, we found that holding in mind an intention to act and at the same time thinking about an intentional action led to reduced activity in a dorsal section of the mPFC. This was a different region from a more anterior, inferior dorsal mPFC region that responded to intentional causality. This suggests that different regions of mPFC play different roles in thinking about intentions. D