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Mindfulness training ameliorates clinical and self-report measures of depression and chronic pain, but its use as an emotion regulation strategy—in individuals who do not meditate—remains understudied. As such, whether it (i) down-regulates early affective brain processes or (ii) depends on cognitive control systems remains unclear. We exposed meditation-naïve participants to two kinds of stimuli: negative vs. neutral images and painful vs. warm temperatures. On alternating blocks, we asked participants to either react naturally or exercise mindful acceptance. Emotion regulation using mindful acceptance was associated with reductions in reported pain and negative affect, reduced amygdala responses to negative images and reduced heat-evoked responses in medial and lateral pain systems. Critically, mindful acceptance significantly reduced activity in a distributed, a priori neurologic signature that is sensitive and specific to experimentally induced pain. In addition, these changes occurred in the absence of detectable increases in prefrontal control systems. The findings support the idea that momentary mindful acceptance regulates emotional intensity by changing initial appraisals of the affective significance of stimuli, which has consequences for clinical treatment of pain and emotion.

BackgroundCognitive behavioral therapy (CBT) is an effective treatment for many patients suffering from major depressive disorder (MDD), but predictors of treatment outcome are lacking, and little is known about its neural mechanisms. We recently identified longitudinal changes in neural correlates of conscious emotion regulation that scaled with clinical responses to CBT for MDD, using a negative autobiographical memory-based task.MethodsWe now examine the neural correlates of emotional reactivity and emotion regulation during viewing of emotionally salient images as predictors of treatment outcome with CBT for MDD, and the relationship between longitudinal change in functional magnetic resonance imaging (fMRI) responses and clinical outcomes. Thirty-two participants with current MDD underwent baseline MRI scanning followed by 14 sessions of CBT. The fMRI task measured emotional reactivity and emotion regulation on separate trials using standardized images from the International Affective Pictures System. Twenty-one participants completed post-treatment scanning. Last observation carried forward was used to estimate clinical outcome for non-completers.ResultsPre-treatment emotional reactivity Blood Oxygen Level-Dependent (BOLD) signal within hippocampus including CA1 predicted worse treatment outcome. In contrast, better treatment outcome was associated with increased down-regulation of BOLD activity during emotion regulation from time 1 to time 2 in precuneus, occipital cortex, and middle frontal gyrus.ConclusionsCBT may modulate the neural circuitry of emotion regulation. The neural correlates of emotional reactivity may be more strongly predictive of CBT outcome. The finding that treatment outcome was predicted by BOLD signal in CA1 may suggest overgeneralized memory as a negative prognostic factor in CBT outcome.

Neuroimaging research has identified systems that facilitate minimizing negative emotion, but how the brain is able to transform the valence of an emotional response from negative to positive is unclear. Behavioral and psychophysiological studies suggest a distinction between minimizing reappraisal, which entails diminishing the arousal elicited by negative stimuli, and positive reappraisal, which instead changes the emotional valence of arousal from negative to positive. Here we show that successful minimizing reappraisal tracked with decreased activity in the amygdala, but successful positive reappraisal tracked with increased activity in regions involved in computing reward value, including the ventral striatum and ventromedial pFC (vmPFC). Moreover, positive reappraisal enhanced positive connectivity between vmPFC and amygdala, and individual differences in positive connectivity between vmPFC and amygdala, ventral striatum, dorsomedial pFC, and dorsolateral pFC predicted greater positive reappraisal success. These data broaden models of emotion regulation as quantitative dampening of negative emotion and identify activity in a network of brain valuation, arousal, and control regions as a neural basis for the ability to create positive meaning from negative experiences.

Suicidal behavior and difficulty regulating emotions are hallmarks of Borderline Personality Disorder (BPD). This study examined neural links between emotion regulation and suicide risk in BPD. 60 individuals with BPD (all female, mean age = 28.9 years), 46 of whom had attempted suicide, completed a fMRI task involving recalling aversive personal memories. Distance trials assessed the ability to regulate emotion by recalling memories from a third-person, objective viewpoint. Immerse trials assessed emotional reactivity and involved recalling memories from a first-person perspective. Behaviorally, both groups reported less negative affect on Distance as compared to Immerse trials. Neurally, two sets of findings were obtained. The first reflected differences between attempters and non-attempters. When immersing and distancing, attempters showed elevated recruitment of lateral orbitofrontal cortex, a brain region implicated in using negative cues to guide behavior. When distancing, attempters showed diminished recruitment of the precuneus, a region implicated in memory recall and perspective taking. The second set of findings related to individual differences in regulation success - the degree to which individuals used distancing to reduce negative affect. Here, we observed that attempters who successfully regulated exhibited precuneus recruitment that was more similar to non-attempters. These data provide insight into mechanisms underlying suicide attempts in BPD. Future work may examine if these findings generalize to other diagnoses and also whether prior findings in BPD differ across attempters and non-attempters.

Can taking the perspective of other people modify our own affective responses to stimuli? To address this question, we examined the neurobiological mechanisms supporting the ability to take another person's perspective and thereby emotionally experience the world as they would. We measured participants' neural activity as they attempted to predict the emotional responses of two individuals that differed in terms of their proneness to experience negative affect. Results showed that behavioral and neural signatures of negative affect (amygdala activity and a distributed multivoxel pattern reflecting affective negativity) simulated the presumed affective state of the target person. Furthermore, the anterior medial prefrontal cortex (mPFC)-a region implicated in mental state inference-exhibited a perspective-dependent pattern of connectivity with the amygdala, and the multivoxel pattern of activity within the mPFC differentiated between the two targets. We discuss the implications of these findings for research on perspective-taking and self-regulation.

Patients with acute myeloid leukemia (AML), who are refractory to induction therapy or experience relapse after a first complete remission (CR), have an unfavorable prognosis.[1][1] Epigenetic dysregulation is frequent in AML. In preclinical studies, the pan-deacetylase inhibitor (DACi) panobinostat

Background Dysregulated autobiographical recall is observed in major depressive disorder (MDD). However, it is unknown whether people with MDD show abnormalities in memory-, emotion-, and control-related brain systems during reactivity to and regulation of negative autobiographical memories. Methods We used functional magnetic resonance imaging to identify neural mechanisms underlying MDD-related emotional responses to negative autobiographical memories and the ability to downregulate these responses using a cognitive regulatory strategy known as reappraisal. We compared currently depressed, medication-free patients with MDD ( n = 29) with control participants with no history of depression ( n = 23). Results Relative to healthy control participants, medication-free MDD patients reported greater negative emotion during recall but relatively intact downregulation success. They also showed elevated amygdala activity and greater amygdala-hippocampal connectivity. This connectivity mediated the effect of MDD on negative emotional experience. When reappraising memories (vs. recalling from an immersed perspective), the MDD and control groups showed comparable recruitment of the prefrontal, parietal, and temporal cortices, and comparable downregulation of the amygdala and anterior hippocampus. However, MDD patients showed greater downregulation of the posterior hippocampus, and the extent of this downregulation predicted successful reduction of negative affect in MDD patients only. Conclusions These data suggest amygdala-hippocampal connectivity and posterior hippocampal downregulation as brain mechanisms related to elevated emotional reactivity and atypical emotion regulation in MDD.

Understanding how and why affective responses change with age is central to characterizing typical and atypical emotional development. Prior work has emphasized the role of the amygdala and prefrontal cortex (PFC), which show age-related changes in function and connectivity. However, developmental neuroimaging research has only recently begun to unpack whether age effects in the amygdala and PFC are specific to affective stimuli or may be found for neutral stimuli as well, a possibility that would support a general, rather than affect-specific, account of amygdala-PFC development. To examine this, 112 individuals ranging from 6 to 23 years of age viewed aversive and neutral images while undergoing fMRI scanning. Across age, participants reported more negative affect and showed greater amygdala responses for aversive than neutral stimuli. However, children were generally more sensitive to both neutral and aversive stimuli, as indexed by affective reports and amygdala responses. At the same time, the transition from childhood to adolescence was marked by a ventral-to-dorsal shift in medial prefrontal responses to aversive, but not neutral, stimuli. Given the role that dmPFC plays in executive control and higher-level representations of emotion, these results suggest that adolescence is characterized by a shift towards representing emotional events in increasingly cognitive terms. Keywords: Emotion, Neurodevelopment, Prefrontal cortex, Amygdala, fMRI

Despite significant advances in understanding how brain networks support working mem- ory (WM) and cognitive control, relatively little is known about how these networks respond when cognitive capabilities are overtaxed. We used a fine-grained manipulation of memory load within a single trial to exceed WM capacity during functional magnetic resonance imaging to investigate how these networks respond to support task performance when WM capacity is exceeded. Analyzing cor- rect trials only, we observed a nonmonotonic (inverted-U) response to WM load throughout the clas- sic WM network (including bilateral dorsolateral prefrontal cortex, posterior parietal cortex, and presupplementary motor areas) that peaked later in individuals with greater WM capacity. We also observed a relative increase in activity in medial anterior prefrontal cortex, posterior cingulate/pre- cuneus, and lateral temporal and parietal regions at the highest WM loads, and a set of predomi- nantly subcortical and prefrontal regions whose activation was greatest at the lowest WM loads. At the individual subject level, the inverted-U pattern was associated with poorer performance while expression of the early and late activating patterns was predictive of better performance. In addition, greater activation in bilateral fusiform gyrus and right occipital lobe at the highest WM loads pre- dicted better performance. These results demonstrate dynamic and behaviorally relevant changes in

Background The ability to self-report on affective experience is essential to both our everyday communication about emotion and our scientific understanding of it. However, the underlying cognitive and neural mechanisms for how people construct statements even as simple as “I feel bad!” remain unclear. We examined whether the neural architecture underlying the ability to make statements about affective experience is composed of distinct functional systems. Methods In a novel functional magnetic neuroimaging paradigm, 20 participants were shown images varying in affective intensity; they were required either to attend to and judge the affective response versus to nonaffective aspects of the stimulus and either to categorize their response into a verbal label or report on a scale that did not require verbal labeling. Results We found that the ability to report on affective states involves (at least) three separable systems, one for directing attention to the affective response and making attributions about it that involves the dorsomedial prefrontal cortex, one for categorizing the response into a verbal label or word that involves the ventrolateral prefrontal cortex, and one sensitive to the intensity of the affective response including the ventral anterior insula and amygdala. Conclusions These results suggest that unified statements about affective experience rely on integrating information from several distinct neural systems. Results are discussed in the context of how disruptions to one or another of these systems may produce unique deficits in the ability to describe affective states and the implications this may hold for clinical populations.

The present neuroimaging study investigated two aspects of difficulties with emotion associated with Borderline Personality Disorder (BPD1): affective lability and difficulty regulating emotion. While these two characteristics have been previously linked to BPD symptomology, it remains unknown whether individual differences in affective lability and emotion regulation difficulties are subserved by distinct neural substrates within a BPD sample. To address this issue, sixty women diagnosed with BPD were scanned while completing a task that assessed baseline emotional reactivity as well as top-down emotion regulation. More affective instability, as measured by the Affective Lability Scale (ALS2), positively correlated with greater amygdala responses on trials assessing emotional reactivity. Greater difficulties with regulating emotion, as measured by the Difficulties with Emotion Regulation Scale (DERS3), was negatively correlated with left inferior frontal gyrus (IFG4) recruitment on trials assessing regulatory ability. These findings suggest that, within a sample of individuals with BPD, greater bottom-up amygdala activity is associated with heightened affective lability. By contrast, difficulties with emotion regulation are related to reduced IFG recruitment during emotion regulation. These results point to distinct neural mechanisms for different aspects of BPD symptomology.

Emotion regulation is a critical life skill that develops throughout childhood and adolescence. Despite this development in emotional processes, little is known about how the underlying brain systems develop with age. This study examined emotion regulation in 112 individuals (aged 6-23 years) as they viewed aversive and neutral images using a reappraisal task. On "reappraisal" trials, participants were instructed to view the images as distant, a strategy that has been previously shown to reduce negative affect. On "reactivity" trials, participants were instructed to view the images without regulating emotions to assess baseline emotional responding. During reappraisal, age predicted less negative affect, reduced amygdala responses and inverse coupling between the ventromedial prefrontal cortex (vmPFC) and amygdala. Moreover, left ventrolateral prefrontal (vlPFC) recruitment mediated the relationship between increasing age and diminishing amygdala responses. This negative vlPFC-amygdala association was stronger for individuals with inverse coupling between the amygdala and vmPFC. These data provide evidence that vmPFC-amygdala connectivity facilitates vlPFC-related amygdala modulation across development.

Human neuroimaging offers a powerful way to connect animal and human research on emotion, with profound implications for psychological science. However, the gulf between animal and human studies remains a formidable obstacle: human studies typically focus on the cortex and a few subcortical regions such as the amygdala, whereas deeper structures such as the brainstem periaqueductal gray (PAG) play a key role in animal models. Here, we directly assessed the role of PAG in human affect by interleaving in a single fMRI session two conditions known to elicit strong emotional responses--physical pain and negative image viewing. Negative affect and PAG activity increased in both conditions. We next examined eight independent data sets, half featuring pain stimulation and half negative image viewing. In sum, these data sets comprised 198 additional participants. We found increased activity in PAG in all eight studies. Taken together, these findings suggest PAG is a key component of human affective responses.

How a visual stimulus is initially categorized as a face by the cortical face-processing network remains largely unclear. In this study we used functional MRI to study the dynamics of face detection in visual scenes by using a paradigm in which scenes containing faces or cars are revealed progressively as they emerge from visual noise. Participants were asked to respond as soon as they detected a face or car during the noise sequence. Among the face-sensitive regions identified based on a standard localizer, a high-level face-sensitive area, the right fusiform face area (FFA), showed the earliest difference between face and car activation. Critically, differential activation in FFA was observed before differential activation in the more posteriorly located occipital face area (OFA). A whole brain analysis confirmed these findings, with a face-sensitive cluster in the right fusiform gyrus being the only cluster showing face preference before successful behavioral detection. Overall, these findings indicate that following generic low-level visual analysis, a face stimulus presented in a gradually revealed visual scene is first detected in the right middle fusiform gyrus, only after which further processing spreads to a network of cortical and subcortical face-sensitive areas (including the posteriorly located OFA). These results provide further evidence for a nonhierarchical organization of the cortical face-processing network.

The ability to control craving for substances that offer immediate rewards but whose long-term consumption may pose serious risks lies at the root of substance use disorders and is critical for mental and physical health. Despite its importance, the neural systems supporting this ability remain unclear. Here, we investigated this issue using functional imaging to examine neural activity in cigarette smokers, the most prevalent substance-dependent population in the United States, as they used cognitive strategies to regulate craving for cigarettes and food. We found that the cognitive down-regulation of craving was associated with ( i ) activity in regions previously associated with regulating emotion in particular and cognitive control in general, including dorsomedial, dorsolateral, and ventrolateral prefrontal cortices, and ( ii ) decreased activity in regions previously associated with craving, including the ventral striatum, subgenual cingulate, amygdala, and ventral tegmental area. Decreases in craving correlated with decreases in ventral striatum activity and increases in dorsolateral prefrontal cortex activity, with ventral striatal activity fully mediating the relationship between lateral prefrontal cortex and reported craving. These results provide insight into the mechanisms that enable cognitive strategies to effectively regulate craving, suggesting that it involves neural dynamics parallel to those involved in regulating other emotions. In so doing, this study provides a methodological tool and conceptual foundation for studying this ability across substance using populations and developing more effective treatments for substance use disorders.

Background Although the ability to adaptively reflect on negative autobiographical experiences without ruminating is critical to mental health, to our knowledge no research has directly examined the neural systems underlying this process. Methods Sixteen participants were scanned using functional magnetic resonance imaging (fMRI) as they focused on negative autobiographical memories using cognitive strategies designed to facilitate (feel strategy) versus undermine (analyze and accept strategies) rumination. Results Two key findings were obtained. First, consistent with prior emotion regulation research using image-based stimuli, left prefrontal activity was observed during the implementation of all three strategies. Second, activity in a network of regions involved in self-referential processing and emotion, including subgenual anterior cingulate cortex and medial prefrontal cortex, was highest in response to the feel strategy and lowest for the accept strategy. This pattern of activation mirrored participants' self-reports of negative affect when engaging in each strategy. Conclusions These findings shed light on the brain regions that distinguish adaptive versus maladaptive forms of reflecting on negative autobiographical memories and offer a novel, ecologically valid route to exploring the neural bases of emotion regulation using fMRI.

Nowadays, lumbar spondylosis is one of the most frequent causes of lower back pain. In order to improve our understanding of the lumbar spine anatomy and functionality over time, we compared the lumbar vertebrae of Neanderthals with those of anatomically modern humans. The fossil record reports on only two Neanderthal skeletons (i.e., Kebara 2 and Shanidar 3, both predating the appearance of modern humans) with full preservation of the entire lumbar spine. Examination of these early hominids showed that they display natural lumbar kyphosis, with only mild degenerative changes of the lumbar spine (ages at death: 30-35 years, Kebara 2; and 35-50 years, Shanidar 3). This finding is highly unexpected since Neanderthals are known to have had extraordinary physical activity due to demanding living conditions. The adult lumbar spines discussed here therefore show no correlation between high physical activity and degenerative spine disease as known from recent times. We speculate that both the kyphosis itself and the massive and heavily muscled skeleton of Neanderthals are causative for the minimal bone degeneration. We conclude that a kyphotic lumbar spine is the natural anatomy in these two Neanderthal individuals. Future research will reveal if this holds true for the entire Neanderthal species.

Number processing recruits a complex network of multiple numerical representations. Usually the components of this network are examined in a between-task approach with the disadvantage of relying upon different instructions, tasks, and inhomogeneous stimulus sets across different studies. A within-task approach may avoid these disadvantages and access involved numerical representations more specifically. In the present study we employed a within-task approach to investigate numerical representations activated in the number bisection task (NBT) using parametric rapid event-related fMRI. Participants were to judge whether the central number of a triplet was also its arithmetic mean (e.g. 23_26_29) or not (e.g. 23_25_29). Activation in the left inferior parietal cortex was associated with the deployment of arithmetic fact knowledge, while activation of the intraparietal cortex indicated more intense magnitude processing, instrumental aspects of calculation and integration of the base-10 structure of two-digit numbers. These results replicate evidence from the literature. Furthermore, activation in the dorsolateral and ventrolateral prefrontal cortex revealed mechanisms of feature monitoring and inhibition as well as allocation of cognitive resources recruited to solve a specific triplet. We conclude that the network of numerical representations should rather be studied in a within-task approach than in varying between-task approaches.

Extrastriate, parietal, and frontal brain regions are differentially involved in distinct kinds of body movements and motor cognition. Using functional magnetic resonance imaging, we investigated the neural mechanisms underlying the observation and mental imagery of meaningful face and limb movements with or without objects. The supplementary motor area was differentially recruited by the mental imagery of movements while there were differential responses of the extrastriate body area (EBA) during the observation conditions. Contrary to most previous reports, the EBA responded to face movements, albeit to a lesser degree than to limb movements. The medial wall of the intraparietal sulcus and adjacent intraparietal cortex was selectively recruited by the processing of meaningful upper limb movements, irrespective of whether these were object‐related or not. Besides reach and grasp movements, the intraparietal sulcus may thus be involved in limb gesture processing, that is, in an important aspect of human social communication. We conclude that subregions of a frontal–parietal network differentially interact during the cognitive processing of body movements according to the specific motor‐related task at hand and the particular movement features involved. Hum Brain Mapp, 2009. © 2007 Wiley‐Liss, Inc.

✓ Spinal tuberculosis (TB) infrequently involves more than one to three vertebrae, and kyphotic angulation of greater than 30° is rare in paleopathological specimens and clinical studies. The authors describe findings obtained in two spines (dating from the Early and Late Middle Ages). Spinal TB was present in both as well as sharply angulated kyphosis (∼ 180°) resulting from complete destruction of five and seven vertebral bodies, respectively. In these two specimens obtained in individuals older than 12 years of age at the time of death we observed no involvement of the disease in posterior vertebral elements, and the laminae showed osseous fusion without signs of infection. The osseous diameter of the spinal canal was not narrowed in either case. These findings are discussed in the context of modern medical knowledge and paleopathological and genetic examinations.

Differences in popularity are a key aspect of status in virtually all human groups and shape social interactions within them. Little is known, however, about how we track and neurally represent others' popularity. We addressed this question in two real-world social networks using sociometric methods to quantify popularity. Each group member (perceiver) viewed faces of every other group member (target) while whole-brain functional MRI data were collected. Independent functional localizer tasks were used to identify brain systems supporting affective valuation (ventromedial prefrontal cortex, ventral striatum, amygdala) and social cognition (dorsomedial prefrontal cortex, precuneus, temporoparietal junction), respectively. During the face-viewing task, activity in both types of neural systems tracked targets' sociometric popularity, even when controlling for potential confounds. The target popularity-social cognition system relationship was mediated by valuation system activity, suggesting that observing popular individuals elicits value signals that facilitate understanding their mental states. The target popularity-valuation system relationship was strongest for popular perceivers, suggesting enhanced sensitivity to differences among other group members' popularity. Popular group members also demonstrated greater interpersonal sensitivity by more accurately predicting how their own personalities were perceived by other individuals in the social network. These data offer insights into the mechanisms by which status guides social behavior.

Primary intraosseous calvarial meningiomas are very rare entities in recent times. We present the first case in antiquity of a primary intraosseous meningioma in the frontoparietal bone associated with the coronal suture, and discuss its pathology. The skull derives from southwestern Germany and is dated to the 12th–14th centuries AD. The lesion is interpreted as a solitary osteoblastic neoplasm with hyperostosis on the outside, and osteolysis and radial spiculation in the central part of the lesion with an area of irregularity along the inner table. In cases of solitary osteoblastic skull lesions the differential diagnosis comprises: fibrous dysplasia, osteoma, osteoblastic metastasis, Pagets disease and meningioma with sheet-like growth along the dural surface with marked hyperostosis (called meningioma en plaque). We believe that a differentiation between hyperostotic meningioma en plaque and intraosseous meningioma cannot be made in skulls from antiquity. Copyright © 2002 John Wiley & Sons, Ltd.

Although one third of children and adolescents are overweight or obese, developmental changes in food craving and the ability to regulate craving remain poorly understood. We addressed this knowledge gap by examining behavioral and neural responses to images of appetizing unhealthy foods in individuals ages 6 through 23 years. On close trials (assessing unregulated craving), participants focused on a pictured food’s appetitive features. On far trials (assessing effortful regulation), participants focused on a food’s visual features and imagined that it was farther away. Across conditions, older age predicted less craving, less striatal recruitment, greater prefrontal activity, and stronger frontostriatal coupling. When effortfully regulating their responses to the images, all participants reported less craving and exhibited greater recruitment of lateral prefrontal cortex and less recruitment of ventromedial prefrontal cortex. Greater body mass predicted less regulation-related prefrontal activity, particularly among children. These results suggest that children experience stronger craving than adults but can also effectively regulate craving. Moreover, the mechanisms underlying regulation may differ for heavy and lean children.

This study used functional MRI (fMRI) to examine a novel aspect of emotion regulation in adolescent development: whether age predicts differences in both the concurrent and lasting effects of emotion regulation on amygdala response. In the first, active regulation, phase of the testing session, fMRI data were collected while 56 healthy individuals (age range: 10.50-22.92 years) reappraised aversive stimuli so as to diminish negative responses to them. After a short delay, the second, re-presentation, phase involved passively viewing the aversive images from the reappraisal task. During active regulation, older individuals showed greater drops in negative affect and inverse rostrolateral prefrontal-amygdala connectivity. During re-presentation, older individuals continued to show lasting reductions in the amygdala response to aversive stimuli they had previously reappraised, an effect mediated by rostrolateral PFC. These data suggest that one source of heightened emotionality in adolescence is a diminished ability to cognitively down-regulate aversive reactions.

One of the most effective strategies for regulating emotional responses is cognitive reappraisal. While prior work has made great strides in characteriz- ing reappraisals neural mechanisms and behavioral outcomes, the key issue of how regulation varies as a function of emotional intensity remains unaddressed. We compared the behavioral and neural correlates of reappraisal of high- and low-intensity emotional responses using functional magnetic resonance imaging (fMRI). We found that successful reappraisal of both high- and low-intensity emotions depends upon recruitment of dorsomedial (dmPFC) as well as left dorsolateral (dlPFC) and ventrolateral (vlPFC) prefrontal cortex. However, reappraisal of high-intensity emotions more strongly activated left dlPFC, and in addition, activated right lateral and dorsomedial PFC regions not recruited by low-intensity reappraisal. No brain regions were more strongly recruited during reappraisal of low when compared with high-intensity emotions. Taken together, these results suggest that reappraisal of high-intensity emotion requires greater cognitive resources as evidenced by quantitative and qualitative differences in prefrontal recruitment. These data have implications for understanding how and when specific PFC systems are needed to regulate different types of emotional responses.

The intentional deformation of human skulls in the living being was one of the most curious rituals performed in historical and ancient times. It is thought that these practices cause chronic elevated intracranial pressure and subsequent symptoms of cognitive impairment. In this report, we examine such an artificially deformed skull dating from the sixteenth century that in addition shows a fronto-ethmoidal encephalocele. However, although the mild encephalocele was already manifest at birth and deformation practices were performed over years, the encephalocele did not progress into a more severe status. We conclude that the intentional deformation of skulls does not lead to chronic elevated intracranial pressure and mental retardation.

In recent years, an explosion of neuroimaging studies has examined cognitive reappraisal, an emotion regulation strategy that involves changing the way one thinks about a stimulus in order to change its affective impact. Existing models broadly agree that reappraisal recruits frontal and parietal control regions to modulate emotional responding in the amygdala, but they offer competing visions of how this is accomplished. One view holds that control regions engage ventromedial prefrontal cortex (vmPFC), an area associated with fear extinction, that in turn modulates amygdala responses. An alternative view is that control regions modulate semantic representations in lateral temporal cortex that indirectly influence emotion-related responses in the amygdala. Furthermore, while previous work has emphasized the amygdala, whether reappraisal influences other regions implicated in emotional responding remains unknown. To resolve these questions, we performed a meta-analysis of 48 neuroimaging studies of reappraisal, most involving downregulation of negative affect. Reappraisal consistently 1) activated cognitive control regions and lateral temporal cortex, but not vmPFC, and 2) modulated the bilateral amygdala, but no other brain regions. This suggests that reappraisal involves the use of cognitive control to modulate semantic representations of an emotional stimulus, and these altered representations in turn attenuate activity in the amygdala.

The use of low-calcium peritoneal dialysis solutions (PDS) for continuous ambulatory peritoneal dialysis is becoming widely accepted to reduce the risk of serum hypercalcemia in patients taking calcium salts as phosphate binders. We compared the in vitro effects of low-calcium PDS (1,000 μmol calcium/L), calcium-free buffer, and buffers with increasing calcium concentrations (500 to 5,000 μmol calcium/L) on peritoneal macrophage (PMO) functions. Peritoneal macrophages isolated from 10 continuous ambulatory peritoneal dialysis patients were incubated in the different solutions and tested for phagocytic and killing capacity, superoxide generation (cytochrome-C reduction and lucigenin-enhanced chemiluminescence), and the rate of myeloperoxidase-dependent oxidative metabolism (luminol-enhanced chemiluminescence). All functions of the PMO incubated in calcium-free buffer were significantly suppressed compared with the PMO incubated in calcium buffers. No dose-dependent increase of a single PMO function could be found after incubating the PMO in calcium buffer with increasing concentrations. Incubation of PMO in otherwise identical PDS containing 1,000, 1,450, or 1,750 μmol calcium/L did not result in significantly different PMO functions. Acidic PDS (pH 5.3 to 5.5) suppressed all measured PMO functions as compared with their neutralized counterparts (pH 7.4), irrespective of the calcium concentration. Results of our in vitro study show that low-calcium PDS does not suppress PMO functions any more than standard-calcium PDS (1,750 μmol calcium/L) does.

Expectations about an upcoming emotional event have the power to shape one’s subsequent affective response for better or worse. Here, we used mediation analyses to examine the relationship between brain activity when anticipating the need to cognitively reappraise aversive images, amygdala responses to those images and subsequent success in diminishing negative affect. We found that anticipatory activity in right rostrolateral prefrontal cortex was associated with greater subsequent left amygdala responses to aversive images and decreased regulation success. In contrast, anticipatory ventral anterior insula activity was associated with reduced amygdala responses and greater reappraisal success. In both cases, left amygdala responses mediated the relationship between anticipatory activity and reappraisal success. These results suggest that anticipation facilitates successful reappraisal via reduced anticipatory prefrontal ‘cognitive’ elaboration and better integration of affective information in paralimbic and subcortical systems.

Human experiences can be broadly divided into those that are external and related to interaction with the environment, and experiences that are internal and self-related. The cerebral cortex appears to be divided into two corresponding systems: an “extrinsic” system composed of brain areas that respond more to external stimuli and tasks and an “intrinsic” system composed of brain areas that respond less to external stimuli and tasks. These two broad brain systems seem to compete with each other, such that their activity levels over time is usually anti-correlated, even when subjects are “at rest” and not performing any task. This study used meditation as an experimental manipulation to test whether this competition (anti-correlation) can be modulated by cognitive strategy. Participants either fixated without meditation (fixation), or engaged in non-dual awareness (NDA) or focused attention (FA) meditations. We computed inter-area correlations (“functional connectivity”) between pairs of brain regions within each system, and between the entire extrinsic and intrinsic systems. Anti-correlation between extrinsic vs. intrinsic systems was stronger during FA meditation and weaker during NDA meditation in comparison to fixation (without mediation). However, correlation between areas within each system did not change across conditions. These results suggest that the anti-correlation found between extrinsic and intrinsic systems is not an immutable property of brain organization and that practicing different forms of meditation can modulate this gross functional organization in profoundly different ways.

Contralateral sensory deficits in Wallenberg's lateral medullary syndrome suggest bilateral processing of trigeminal afferent input in the human brainstem. On the basis of experiments in rodents and clinical data, the present study addresses the hypothesis of bilateral projection of facial nociceptive input onto the spinal trigeminal nucleus (STN) in healthy humans. Nociceptive processing in the brainstem was investigated by functional magnetic resonance imaging (fMRI) in 18 healthy volunteers. Heat stimuli (39, 43, 46 degrees C) were applied by a Peltier type thermode to the left forehead (V1) and the left mental region (V3). Analyses of fMRI data were performed with SPM2 and BrainVoyager software. A region-of-interest approach analyzed local activation in the STN. Heat evoked significant bilateral activation in the STN (P0.01, T2.8). Contralateral activation was more frequent during stimulation of the V1 than of the V3 region. Whereas activation by V1 stimulation was located in caudal STN, V3 stimulation induced activity in more rostral parts of the STN. Functional MRI data in humans suggest bilateral brainstem activation when heat is applied to the face. Contralateral brainstem activity is more pronounced by stimulation of V1 as compared to V3. The results indicate similar nociceptive processing in humans and rodents and may explain clinical findings.

Alarm substances are airborne chemical signals, released by an individual into the environment, which communicate emotional stress between conspecifics. Here we tested whether humans, like other mammals, are able to detect emotional stress in others by chemosensory cues. Sweat samples collected from individuals undergoing an acute emotional stressor, with exercise as a control, were pooled and presented to a separate group of participants (blind to condition) during four experiments. In an fMRI experiment and its replication, we showed that scanned participants showed amygdala activation in response to samples obtained from donors undergoing an emotional, but not physical, stressor. An odor-discrimination experiment suggested the effect was primarily due to emotional, and not odor, differences between the two stimuli. A fourth experiment investigated behavioral effects, demonstrating that stress samples sharpened emotion-perception of ambiguous facial stimuli. Together, our findings suggest human chemosensory signaling of emotional stress, with neurobiological and behavioral effects.

Alarm pheromones are airborne chemical signals, released by an individual into the environment, which transmit warning of danger to conspecifics via olfaction. Using fMRI, we provide the first neurobiological evidence for a human alarm pheromone. Individuals showed activation of the amygdala in response to sweat produced by others during emotional stress, with exercise sweat as a control; behavioral data suggest facilitated evaluation of ambiguous threat.

Neurofunctional alterations in acute posttraumatic stress disorder (PTSD) and changes thereof during the course of the disease are not well investigated. We used functional magnetic resonance imaging to assess the functional neuroanatomy of emotional memory in surgical patients with acute PTSD. Traumatic (relative to non-traumatic) memories increased neural activity in the amygdala, hippocampus, lateral temporal, retrosplenial, and anterior cingulate cortices. These regions are all implicated in memory and emotion. A comparison of findings with data on chronic PTSD suggests that brain circuits affected by the acute disorder are extended and unstable while chronic disease is characterized by circumscribed and stable neurofunctional abnormalities.

In the present study, we were interested in distinguishing the cortical representations of within‐modal and cross‐modal divided attention tasks by using functional magnetic resonance imaging. Sixteen healthy male subjects aged between 21 and 30 years underwent two within‐modal (auditory/auditory, visual/visual) and one cross‐modal (auditory/visual) divided attention task, as well as related selective attention control conditions. After subtraction of the corresponding control task the three divided attention tasks, irrespective of sensory modality, revealed significant activation in a predominantly right hemisphere network involving the prefrontal cortex, the inferior parietal cortex, and the claustrum. Under the cross‐modal condition, however, the frontal and parietal activation was more extended and more bilateral and there also was stronger right hemisphere activation of the anterior cingulate cortex and the thalamus. In comparison to the within‐modal conditions additional bilateral frontal and left inferior parietal activation was found for the cross‐modal condition. The supplementary fronto‐parietal, anterior cingulate cortex, and thalamus activation in the auditory/visual condition could be argued to reflect an additional demand for coordination of two ongoing cross‐modal cognitive processes. Hum Brain Mapp, 2007. © 2007 Wiley‐Liss, Inc.

OBJECTIVE Trauma and degenerative joint disease are the most common pathological conditions observed in archaeological skeletal remains. We describe the prevalence of different types of cervical bone diseases observed in the early Middle Ages (6th to 8th centuries AD). METHODS Human skeletons were excavated from Germanic row graves in southwestern Germany. One hundred ninety-six cervical spines thus obtained were examined for bone disease. The degenerative changes were classified into Grades 1 (marginal osteophytes), 2 (uneven joint surfaces), and 3 (osseous ankylosis). Cervical spinal canal stenosis was defined as anteroposterior diameters of RESULTS Of the skeletons, 27.5% demonstrated degenerative changes of the cervical spine. The mean age of the skeletons at the time of death was 33.4 years, compared with 43.7 years for those with degenerative disease. Degenerative changes of the vertebral bodies (usually Grades 1 and 2) were most common in the C5–C6 (12.4%, P < 0.05) and C6–C7 (15.3%, P < 0.05) segments. The medial (6.1%) and lateral (0.6%) atlantoaxial joints were rarely involved in degenerative disease. The facet joints from C3–C4 to C6–C7 demonstrated degenerative changes (usually Grades 1 and 2) in 8.0 to 11.8% of cases. The C2–C3 facet joints were significantly involved in degenerative disease in 19.7% of cases (P < 0.05), one-fourth of which demonstrated osseous ankylosis. We observed cervical spinal canal stenosis in 5 skeletons (2.6%) and osseous intervertebral foraminal stenoses in 12 (6.1%). Isolated cases of other pathological processes, i.e., spondylitis ankylopoietica, occipitalization of the atlas and axis, and an odontoid fracture with pseudoarthrosis, were also recorded. CONCLUSION In the early Middle Ages, the prevalence of degenerative cervical spine disease was the same as that observed today. The C2–C3 facet joints demonstrated high rates of degenerative disease.

Approximately 10% (33 of 304) of the predominantly male skulls from the 6th through 8th centuries in southwestern Germany exhibit cranial fractures derived from blunt or sharp force trauma. No evidence of fracture healing characterizes 24% (n = 8) of these individuals. All nonhealed fractures were caused by sharp force, and four of these wounds cross the sagittal sinus. The lengths of these straight-edged wounds, produced exclusively by sword blows, measure around 8.0 cm for fatal, and about 5.0 cm for nonfatal wounds. Seventy-six percent (n = 25) of these skulls exhibit some healing, which indicates that these injuries did not lead to immediate death. In this group are all depressed fractures resulting from blunt force blows. Two thirds of the 45 cranial injuries noted on these 33 skulls are located on the left side of these individuals, with a concentration in the frontoparietal region. Bony indications of wound infection occur in four cases (12%). Three crania exhibit circular trepanations in association with fractures. These phenomena are discussed in the context of modern neurotraumatological knowledge.

Skin biopsies of 33 uremic patients-13 patients on continuous ambulatory peritoneal dialysis (CAPD), 12 on hemodialysis (HD), 8 patients with end-stage renal disease (ESRD) before initiation of dialysis treatment-and 10 healthy volunteers were investigated to determine the number of Langerhans cells (LC) by light microscopy after staining for S-100 protein. The epidermal LC count was significantly lower in patients on CAPD (mean: 62.9 LC/mm2; p = 0.027) and patients on HD (mean: 30.4 LC/mm2; p = 0.0015) compared to controls (mean: 110.1 LC/mm2) and uremic patients before initiation of dialysis treatment (mean: 122.6 LC/mm2). The difference between LC counts of CAPD and HD patients did not reach statistical significance (p = 0.057). There was no relation between LC count and age (p = 0.057) or epidermal width (p = 0.26). No statistically significant correlation could be demonstrated between duration of dialysis and LC count (r = -0.33, p = 0.10). LC counts of CAPD patients with diabetes mellitus (n = 7) were not significantly different from those of nondiabetics (n = 6; p = 0.77). LC counts seem to be normal in uremic patients before dialysis treatment. The reduction in LC density in the skin of dialysis patients may contribute to immunodeficiency of uremic patients on regular dialysis treatment.

In vivo effect of 1,25-dihydroxyvitamin D 3 on phagocyte function in hemodialysis patients. 1,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] has been shown to modulate the immune function of monocytes and macrophages. Patients with end-stage renal disease (ESRD) on chronic hemodialysis treatment usually present a deficiency of this active form of vitamin D 3 . The aim of this study was to investigate the effect of 1,25(OH) 2 D 3 replacement therapy on phagocytosis, bactericidal capacity, and oxidative metabolism of peripheral blood polymorphonuclear leukocytes (PMNL) and monocytes (MN) in chronic hemodialysis patients. Phagocyte function tests were performed before and after four weeks of an oral replacement therapy with 0.5 µg/day of 1,25(OH) 2 D 3 (Rocaltrol®). The superoxide (O 2 - ) generation of monocytes, measured by cytochrome c reduction and lucigenin-enhanced chemiluminescence (CL) from patients receiving hemodialysis treatment was significantly diminished compared to healthy controls. After the replacement therapy with 1,25(OH) 2 D 3 the O 2 - production showed a significant improvement, resulting in an increased cytochrome c reduction and lucigenin-CL response. The bactericidal capacity of MN was also impaired and exhibited a significant enhancement of their killing activity after the administration of 1,25(OH) 2 D 3 . On the other hand, the luminol-enhanced CL, which reflects the myeloperoxidase-dependent oxidative metabolism, and the phagocytic ability of MN was not affected by the hormone. The function of polymorphonuclear leukocytes (PMNL) from hemodialysis patients showed no impairment in the state of 1,25(OH) 2 D 3 deficiency and the replacement of the hormone did not enhance their function. These results suggest that the deficiency of 1,25(OH) 2 D 3 in patients with ESRD on chronic hemodialysis treatment may be responsible for an impaired monocyte function, which could be improved by an in vivo replacement of the hormone.