Rapid generation of maturationally synchronized human dendritic cells: contribution to the clinical efficacy of extracorporeal photochemotherapy.

Extracorporeal photochemotherapy (ECP) is widely used to treat cutaneous T-cell lymphoma, graft-versus-host disease, and allografted organ rejection. Its clinical and experimental efficacy in cancer immunotherapy and autoreactive disorders suggests a novel mechanism. This study reveals that ECP induces a high percentage of processed monocytes to enter the antigen-presenting dendritic cell (DC) differentiation pathway, within a single day, without added cytokines, as determined by enhanced expression of relevant genes. The resulting DCs are capable of processing and presentation of exogenous and endogenous antigen and are largely maturationally synchronized, as assessed by the level of expression of costimulatory surface molecules. Principal component analysis of the ECP-induced monocyte transcriptome reveals that activation or suppression of more than 1100 genes produces a reproducible distinctive molecular signature, common to ECP-processed monocytes from normal subjects, and those from patients. Because ECP induces normal monocytes to enter the DC differentiation pathway, this phenomenon is independent of disease state. The efficiency with which ECP stimulates new functional DCs supports the possibility that these cells participate prominently in the clinical successes of the treatment. Appropriately modified by future advances, ECP may potentially offer a general source of therapeutic DCs.

An fMRI investigation of the impact of interracial contact on executive function.

We investigated whether individual differences in racial bias among white participants predict the recruitment, and potential depletion, of executive attentional resources during contact with black individuals. White individuals completed an unobtrusive measure of racial bias, then interacted with a black individual, and finally completed an ostensibly unrelated Stroop color-naming test. In a separate functional magnetic resonance imaging (fMRI) session, subjects were presented with unfamiliar black male faces, and the activity of brain regions thought to be critical to executive control was assessed. We found that racial bias predicted activity in right dorsolateral prefrontal cortex (DLPFC) in response to black faces. Furthermore, activity in this region predicted Stroop interference after an actual interracial interaction, and it statistically mediated the relation between racial bias and Stroop interference. These results are consistent with a resource depletion account of the temporary executive dysfunction seen in racially biased individuals after interracial contact.

Differential role of the orbital frontal lobe in emotional versus cognitive perspective-taking.

Lesions of the orbital frontal lobe, particularly its medial sectors, are known to cause deficits in empathic ability, whereas the role of this region in theory of mind processing is the subject of some controversy. In a functional magnetic resonance imaging study with healthy participants, emotional perspective-taking was contrasted with cognitive perspective-taking in order to examine the role of the orbital frontal lobe in subcomponents of theory of mind processing. Subjects responded to a series of scenarios presented visually in three conditions: emotional perspective-taking, cognitive perspective-taking and a control condition that required inferential reasoning, but not perspective-taking. Group results demonstrated that the medial orbitofrontal lobe, defined as Brodmann's areas 11 and 25, was preferentially involved in emotional as compared to cognitive perspective-taking. This finding is both consistent with the lesion literature, and resolves the inconsistency of orbital frontal findings in the theory of mind literature.

Functional differences among those high and low on a trait measure of psychopathy.

BACKGROUND: It has been established that individuals who score high on measures of psychopathy demonstrate difficulty when performing tasks requiring the interpretation of other's emotional states. The aim of this study was to elucidate the relation of emotion and cognition to individual differences on a standard psychopathy personality inventory (PPI) among a nonpsychiatric population. METHODS: Twenty participants completed the PPI. Following survey completion, a mean split of their scores on the emotional-interpersonal factor was performed, and participants were placed into a high or low group. Functional magnetic resonance imaging data were collected while participants performed a recognition task that required attention be given to either the affect or identity of target stimuli. RESULTS: No significant behavioral differences were found. In response to the affect recognition task, significant differences between high- and low-scoring subjects were observed in several subregions of the frontal cortex, as well as the amygdala. No significant differences were found between the groups in response to the identity recognition condition. CONCLUSIONS: Results indicate that participants scoring high on the PPI, although not behaviorally distinct, demonstrate a significantly different pattern of neural activity (as measured by blood oxygen level-dependent contrast)in response to tasks that require affective processing. The results suggest a unique neural signature associated with personality differences in a nonpsychiatric population.

Cognitive control reduces sensitivity to relational aggression among adolescent girls.

Relational aggression is a type of aggression that aims to hurt others through relationships and includes behaviors such as gossip and ostracism. This type of aggression is very common among adolescent girls, and in its more intense forms has been linked with poor psychosocial outcomes, including depression and suicide. In the present study we investigated whether individual differences in sensitivity to relational aggression among adolescent girls predicted recruitment of neural networks associated with executive function and cognitive control. Neural response was measured using functional magnetic resonance imaging during an affect recognition task that included unfamiliar peer faces. A finding of relatively fewer reports of being victimized by relational aggression was associated with increased recruitment of bilateral dorsolateral prefrontal cortices as well as anterior and posterior cingulate cortices in response to the affect recognition task, as well as with greater competence on behavioral measures of executive function. Our results suggest that girls who are able to recruit specific frontal networks to improve cognitive and executive control are less sensitive to relational aggression.

Attending to Threat: Race-based Patterns of Selective Attention.

The present research investigated the extent to which the stereotype that young Black men are threatening and dangerous has become so robust and ingrained in the collective American unconscious that Black men now capture attention, much like evolved threats such as spiders and snakes. Specifically, using a dot-probe detection paradigm, White participants revealed biased attention toward Black faces relative to White faces (Study 1). Because the faces were presented only briefly (30-ms), the bias is thought to reflect the early engagement of attention. The attentional bias was eliminated, however, when the faces displayed averted eye-gaze (Study 2). That is, when the threat communicated by the Black faces was attenuated by a relevant, competing socio-emotional cue- in this case, averted eye-gaze-they no longer captured perceivers' attention. Broader implications for social cognition, as well as public policies that reify these prevailing perceptions of young Black men are discussed.

COOH-terminal binding protein regulates expression of the p16INK4A tumor suppressor and senescence in primary human cells.

The p16/pocket-protein pathway sets a balance between tumor suppression and capacity for tissue regeneration. Understanding the upstream signaling pathway that turns on the expression of p16 is required both for knowing the tumorigenic stresses from which this pathway provides protection and for appreciating the selective pressure that leads to the loss of this pathway in most human tumors. We report that COOH-terminal binding protein (CtBP), a physiologically regulated transcriptional corepressor that dimerizes to hold together repressive complexes, regulates p16 expression in primary human fibroblasts and keratinocytes. Interfering with CtBP-mediated repression increased p16 expression and accelerated senescence. CtBP had little influence on the expression of the alternate product of the CDKN2A tumor-suppressor gene, p14(ARF). Loss of CtBP-mediated repression diminished the Polycomb-based epigenetic histone mark that is reported to favor silencing of p16 via DNA methylation. Enhancing CtBP-mediated repression by growing cells in low oxygen increased the association of CtBP with the p16 promoter, as assessed by chromatin immunoprecipitation, and reduced p16 expression. Stresses and stimuli that reduce CtBP-mediated repression are associated with increased p16 expression; therefore, CtBP may provide a common final target for regulating the balance among tumor suppression, regenerative capacity, and senescence.

Anatomical changes in the emerging adult brain: a voxel-based morphometry study.

Research has consistently confirmed changes occur in brain morphometry between adolescence and adulthood. The purpose of the present study was to explore anatomical change during a specific environmental transition. High-resolution T1-weighted structural magnetic resonance imaging (MRI) scans were acquired from 19 participants (mean age at initial scan = 18.6 years) during their freshman year. Scans were completed during the fall term and 6 months later before the conclusion of the school year. Voxel-based morphometry was used to assess within-subject change. Significant intensity increases were observed along the right midcingulate, inferior anterior cingulate gyrus, right caudate head, right posterior insula, and bilateral claustrum. Regional changes were not observed in two control groups; one controlling for method and another controlling for age-specific change over time. The results suggest that significant age-related changes in brain structure continue after the age of 18 and may represent dynamic changes related to new environmental challenges. Findings from the regions of change are discussed in the context of specific environmental demands during a period of normative maturation.

Developmental precipitants of borderline personality disorder.

Traditional theories regarding the etiology of borderline personality disorder have focused on poor attachment figures and/or traumatic experience. The present review posits an additional pathogenic course for this disorder. Specifically, the proposed mechanism involves a basic disruption of the neural hardware that supports the formation and maintenance of unconscious emotional memory, hardware essential for the formation of early attachments. It is further theorized that this early disruption has ongoing effects on both behavioral and concomitant neural development. Within this model, adolescence is described as a period of intense change that serves as the tipping point for the onset of borderline personality disorder.

Functional connectivity: integrating behavioral, diffusion tensor imaging, and functional magnetic resonance imaging data sets.

In the present study, we combined 2 types of magnetic resonance technology to explore individual differences on a task that required the recognition of objects presented from unusual viewpoints. This task was chosen based on previous work that has established the necessity of information transfer from the right parietal cortex to the left inferior cortex for its successful completion. We used reaction times (RTs) to localize regions of cortical activity in the superior parietal and inferior frontal regions (blood oxygen level-dependent [BOLD] response) that were more active with longer response times. These regions were then sampled, and their signal change used to predict individual differences in structural integrity of white matter in the corpus callosum (using diffusion tensor imaging). Results show that shorter RTs (and associated increases in BOLD response) are associated with increased organization in the splenium of the corpus callosum, whereas longer RTs are associated with increased organization in the genu.

The emergence of consequential thought: evidence from neuroscience.

The ability to think counterfactually about the consequence of one's actions represents one of the hallmarks of the development of complex reasoning skills. The legal system places a great emphasis on this type of reasoning ability as it directly relates to the degree to which individuals may be judged liable for their actions. In the present paper, we review both behavioural and neuroscientific data exploring the role that counterfactual thinking plays in reasoning about the consequences of one's actions, especially as it pertains to the developing mind of the adolescent. On the basis of assimilation of both behavioural and neuroscientific data, we propose a brain-based model that provides a theoretical framework for understanding the emergence of counterfactual reasoning ability in the developing mind.

Frontal lobe activation during object permanence: data from near-infrared spectroscopy.

The ability to create and hold a mental schema of an object is one of the milestones in cognitive development. Developmental scientists have named the behavioral manifestation of this competence object permanence. Convergent evidence indicates that frontal lobe maturation plays a critical role in the display of object permanence, but methodological and ethical constrains have made it difficult to collect neurophysiological evidence from awake, behaving infants. Near-infrared spectroscopy provides a noninvasive assessment of changes in oxy- and deoxyhemoglobin and total hemoglobin concentration within a prescribed region. The evidence described in this report reveals that the emergence of object permanence is related to an increase in hemoglobin concentration in frontal cortex.

Overt propositional speech in chronic nonfluent aphasia studied with the dynamic susceptibility contrast fMRI method.

This study examined activation levels in the left (L) supplementary motor area (SMA) and the right (R) SMA (separately), and activation in nine R perisylvian language homologues during overt, propositional speech in chronic nonfluent aphasia patients. Previous functional imaging studies with a variety of chronic aphasia patients have reported activation in these regions during different language tasks, however, overt propositional speech has not been examined. In the present research, four nonfluent aphasia patients were studied during overt elicited propositional speech at 4-9 years post-single L hemisphere stroke, which spared the SMA. The dynamic susceptibility contrast (DSC) method of functional MRI was used to calculate relative cerebral blood volume (relCBV) for cortical regions of interest (ROIs) during the first-pass bolus of gadolinium during two conditions: (1) pattern (silent viewing of checkerboard patterns) and (2) story (overt, elicited propositional speech describing sequential pictures, which formed a story). During the story condition, controls had significantly higher relCBV in L SMA than in R SMA; aphasics, however, had significantly higher relCBV in R SMA than in L SMA. During the pattern condition, no significant differences were observed between the L SMA and the R SMA for either controls or aphasics. In addition, aphasics had significantly higher relCBV in the R sensorimotor mouth during story than pattern. This R sensorimotor mouth relCBV was also significantly higher in aphasics than controls during story, and the two groups did not differ during pattern. The overall mean relCBV for the nine R perisylvian ROIs was significantly higher for aphasics than controls during both story and pattern. These results suggest that poor modulation, including possible over-activation of R sensorimotor mouth and other R perisylvian language homologues may underlie in part, the hesitant, poorly articulated, agrammatic speech associated with nonfluent aphasia.