Outcomes of Decompressive Surgery for Patients With Severe Cerebral Venous Thrombosis: DECOMPRESS2 Observational Study.

BACKGROUND: Decompressive neurosurgery is recommended for patients with cerebral venous thrombosis (CVT) who have large parenchymal lesions and impending brain herniation. This recommendation is based on limited evidence. We report long-term outcomes of patients with CVT treated by decompressive neurosurgery in an international cohort. METHODS: DECOMPRESS2 (Decompressive Surgery for Patients With Cerebral Venous Thrombosis, Part 2) was a prospective, international cohort study. Consecutive patients with CVT treated by decompressive neurosurgery were evaluated at admission, discharge, 6 months, and 12 months. The primary outcome was death or severe disability (modified Rankin Scale scores, 5-6) at 12 months. The secondary outcomes included patient and caregiver opinions on the benefits of surgery. The association between baseline variables before surgery and the primary outcome was assessed by multivariable logistic regression. RESULTS: A total of 118 patients (80 women; median age, 38 years) were included from 15 centers in 10 countries from December 2011 to December 2019. Surgery (115 craniectomies and 37 hematoma evacuations) was performed within a median of 1 day after diagnosis. At last assessment before surgery, 68 (57.6%) patients were comatose, fixed dilated pupils were found unilaterally in 27 (22.9%) and bilaterally in 9 (7.6%). Twelve-month follow-up data were available for 113 (95.8%) patients. Forty-six (39%) patients were dead or severely disabled (modified Rankin Scale scores, 5-6), of whom 40 (33.9%) patients had died. Forty-two (35.6%) patients were independent (modified Rankin Scale scores, 0-2). Coma (odds ratio, 2.39 [95% CI, 1.03-5.56]) and fixed dilated pupil (odds ratio, 2.22 [95% CI, 0.90-4.92]) were predictors of death or severe disability. Of the survivors, 56 (78.9%) patients and 61 (87.1%) caregivers expressed a positive opinion on surgery. CONCLUSIONS: Two-thirds of patients with severe CVT were alive and more than one-third were independent 1 year after decompressive surgery. Among survivors, surgery was judged as worthwhile by 4 out of 5 patients and caregivers. These results support the recommendation to perform decompressive neurosurgery in patients with CVT with impending brain herniation.

International Skin Imaging Collaboration-Designated Diagnoses (ISIC-DX): Consensus terminology for lesion diagnostic labeling.

BACKGROUND: A common terminology for diagnosis is critically important for clinical communication, education, research and artificial intelligence. Prevailing lexicons are limited in fully representing skin neoplasms. OBJECTIVES: To achieve expert consensus on diagnostic terms for skin neoplasms and their hierarchical mapping. METHODS: Diagnostic terms were extracted from textbooks, publications and extant diagnostic codes. Terms were hierarchically mapped to super-categories (e.g. 'benign') and cellular/tissue-differentiation categories (e.g. 'melanocytic'), and appended with pertinent-modifiers and synonyms. These terms were evaluated using a modified-Delphi consensus approach. Experts from the International-Skin-Imaging-Collaboration (ISIC) were surveyed on agreement with terms and their hierarchical mapping; they could suggest modifying, deleting or adding terms. Consensus threshold was >75% for the initial rounds and >50% for the final round. RESULTS: Eighteen experts completed all Delphi rounds. Of 379 terms, 356 (94%) reached consensus in round one. Eleven of 226 (5%) benign-category terms, 6/140 (4%) malignant-category terms and 6/13 (46%) indeterminate-category terms did not reach initial agreement. Following three rounds, final consensus consisted of 362 terms mapped to 3 super-categories and 41 cellular/tissue-differentiation categories. CONCLUSIONS: We have created, agreed upon, and made public a taxonomy for skin neoplasms and their hierarchical mapping. Further study will be needed to evaluate the utility and completeness of the lexicon.

Prestimulus Activity in the Cingulo-Opercular Network Predicts Memory for Naturalistic Episodic Experience.

Human memory is strongly influenced by brain states occurring before an event, yet we know little about the underlying mechanisms. We found that activity in the cingulo-opercular network (including bilateral anterior insula [aI] and anterior prefrontal cortex [aPFC]) seconds before an event begins can predict whether this event will subsequently be remembered. We then tested how activity in the cingulo-opercular network shapes memory performance. Our findings indicate that prestimulus cingulo-opercular activity affects memory performance by opposingly modulating subsequent activity in two sets of regions previously linked to encoding and retrieval of episodic information. Specifically, higher prestimulus cingulo-opercular activity was associated with a subsequent increase in activity in temporal regions previously linked to encoding and with a subsequent reduction in activity within a set of regions thought to play a role in retrieval and self-referential processing. Together, these findings suggest that prestimulus attentional states modulate memory for real-life events by enhancing encoding and possibly by dampening interference from competing memory substrates.

Neural predictors and effects of cognitive behavioral therapy for depression: the role of emotional reactivity and regulation.

BACKGROUND: Cognitive 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. METHODS: We 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. RESULTS: Pre-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. CONCLUSIONS: CBT 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.

Self-regulation via neural simulation.

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.

Neural Predictors of Decisions to Cognitively Control Emotion.

Deciding to control emotional responses is a fundamental means of responding to environmental challenges, but little is known about the neural mechanisms that predict the outcome of such decisions. We used fMRI to test whether human brain responses during initial viewing of negative images could be used to predict decisions to regulate affective responses to those images. Our results revealed the following: (1) decisions to regulate were more frequent in individuals exhibiting higher average levels of activity within the amygdala and regions of PFC known a priori to be involved in the cognitive control of emotion and (2) within-person expression of a distributed brain pattern associated with regulating emotion predicted choosing to regulate responses to particular stimuli beyond the predictive value of stimulus intensity or self-reports of emotion. These results demonstrate the behavioral relevance of variability in brain responses to aversive stimuli and provide a model that leverages this variability to predict behavior.SIGNIFICANCE STATEMENT Everyone experiences stressors, but how we respond to them can range from protracted disability to resilience and growth. One key process underlying this variability is the agentic decision to exert control over emotional responses. We present an fMRI-based model predicting decisions to control emotion, finding that activity in brain regions associated with the generation and regulation of emotion was predictive of which people choose to regulate frequently and a distributed brain pattern associated with regulating emotion was predictive of which stimuli regulation was chosen. These brain variables predicted future decisions to regulate emotion beyond what could be predicted from stimulus and self-report variables.

vlPFC-vmPFC-Amygdala Interactions Underlie Age-Related Differences in Cognitive Regulation of Emotion.

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.

Neural mechanisms tracking popularity in real-world social networks.

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.

Finding Positive Meaning in Negative Experiences Engages Ventral Striatal and Ventromedial Prefrontal Regions Associated with Reward Valuation.

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.

The Brain Basis of Positive and Negative Affect: Evidence from a Meta-Analysis of the Human Neuroimaging Literature.

The ability to experience pleasant or unpleasant feelings or to represent objects as "positive" or "negative" is known as representing hedonic "valence." Although scientists overwhelmingly agree that valence is a basic psychological phenomenon, debate continues about how to best conceptualize it scientifically. We used a meta-analysis of 397 functional magnetic resonance imaging (fMRI) and positron emission tomography studies (containing 914 experimental contrasts and 6827 participants) to test 3 competing hypotheses about the brain basis of valence: the bipolarity hypothesis that positive and negative affect are supported by a brain system that monotonically increases and/or decreases along the valence dimension, the bivalent hypothesis that positive and negative affect are supported by independent brain systems, and the affective workspace hypothesis that positive and negative affect are supported by a flexible set of valence-general regions. We found little evidence for the bipolar or bivalent hypotheses. Findings instead supported the hypothesis that, at the level of brain activity measurable by fMRI, valence is flexibly implemented across instances by a set of valence-general limbic and paralimbic brain regions.

An initial fMRI study on neural correlates of prayer in members of Alcoholics Anonymous.

BACKGROUND: Many individuals with alcohol-use disorders who had experienced alcohol craving before joining Alcoholics Anonymous (AA) report little or no craving after becoming long-term members. Their use of AA prayers may contribute to this. Neural mechanisms underlying this process have not been delineated. OBJECTIVE: To define experiential and neural correlates of diminished alcohol craving following AA prayers among members with long-term abstinence. METHODS: Twenty AA members with long-term abstinence participated. Self-report measures and functional magnetic resonance imaging of differential neural response to alcohol-craving-inducing images were obtained in three conditions: after reading of AA prayers, after reading irrelevant news, and with passive viewing. Random-effects robust regressions were computed for the main effect (prayer > passive + news) and for estimating the correlations between the main effect and the self-report measures. RESULTS: Compared to the other two conditions, the prayer condition was characterized by: less self-reported craving; increased activation in left-anterior middle frontal gyrus, left superior parietal lobule, bilateral precuneus, and bilateral posterior middle temporal gyrus. Craving following prayer was inversely correlated with activation in brain areas associated with self-referential processing and the default mode network, and with characteristics reflecting AA program involvement. CONCLUSION: AA members' prayer was associated with a relative reduction in self-reported craving and with concomitant engagement of neural mechanisms that reflect control of attention and emotion. These findings suggest neural processes underlying the apparent effectiveness of AA prayer.

Posttranslational proteolytic processing of Leda-1/Pianp involves cleavage by MMPs, ADAM10/17 and gamma-secretase.

Leda-1/Pianp is a type I transmembrane protein expressed by CNS cells, murine melanoma cell line B16F10 and rat liver sinusoidal endothelial cells. The early steps of posttranslational modifications of Leda-1/Pianp have been described to include glycosylation and processing by proprotein convertases. Here, we comprehensively characterized the subsequent steps of proteolytic processing of Leda-1/Pianp. For this purpose specific protease inhibitors and cell lines deficient in PS1, PS2, PS1/PS2 and ADAM10/17 were deployed. Leda-1/Pianp was cleaved at numerous cleavage sites within the N-terminal extracellular domain. The sheddases involved included MMPs and ADAM10/17. Ectodomain shedding yielded C-terminal fragments (CTF) of ∼15 kDa. The CTF was further processed by the γ (gamma)-secretase complex to generate the intracellular domain (ICD) of ∼10 kDa. Although PS1 was the dominant intramembrane protease, PS2 was also able to cleave Leda-1/Pianp in the absence of PS1. Thus, Leda-1/Pianp is constitutively processed by proprotein convertases, sheddases including MMPs and ADAM10/17 and intramembrane protease γ-secretase.

Emotions in "Black and White" or Shades of Gray? How We Think About Emotion Shapes Our Perception and Neural Representation of Emotion.

The demands of social life often require categorically judging whether someone's continuously varying facial movements express "calm" or "fear," or whether one's fluctuating internal states mean one feels "good" or "bad." In two studies, we asked whether this kind of categorical, "black and white," thinking can shape the perception and neural representation of emotion. Using psychometric and neuroimaging methods, we found that (a) across participants, judging emotions using a categorical, "black and white" scale relative to judging emotions using a continuous, "shades of gray," scale shifted subjective emotion perception thresholds; (b) these shifts corresponded with activity in brain regions previously associated with affective responding (i.e., the amygdala and ventral anterior insula); and (c) connectivity of these regions with the medial prefrontal cortex correlated with the magnitude of categorization-related shifts. These findings suggest that categorical thinking about emotions may actively shape the perception and neural representation of the emotions in question.

Inferences of Others' Competence Reduces Anticipation of Pain When under Threat.

On a daily basis, we place our lives in the hands of strangers. From dentists to pilots, we make inferences about their competence to perform their jobs and consequently to keep us from harm. Here we explore whether the perceived competence of others can alter one's anticipation of pain. In two studies, participants (Receivers) believed their chances of experiencing an aversive stimulus were directly dependent on the performance of another person (Players). We predicted that perceiving the Players as highly competent would reduce Receivers' anxiety when anticipating the possibility of an electric shock. Results confirmed that high competence ratings consistently corresponded with lower reported anxiety, and complementary fMRI data showed that increased competence perception was further expressed as decreased activity in the bilateral posterior insula, a region localized to actual pain stimulation. These studies suggest that inferences of competence act as predictors of protection and reduce the expectation of negative outcomes.

Dynamic shifts in brain network activation during supracapacity working memory task performance.

Despite significant advances in understanding how brain networks support working memory (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 correct trials only, we observed a nonmonotonic (inverted-U) response to WM load throughout the classic 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/precuneus, and lateral temporal and parietal regions at the highest WM loads, and a set of predominantly 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 predicted better performance. These results demonstrate dynamic and behaviorally relevant changes in the level of activation of multiple brain networks in response to increasing WM load that are not well accounted for by present models of how the brain subserves the cognitive ability to hold and manipulate information on-line.

Counter-regulation of the ligand-receptor pair Leda-1/Pianp and Pilrα during the LPS-mediated immune response of murine macrophages.

Liver endothelial differentiation-associated protein-1 (Leda-1/Pianp) is a type-I-transmembrane protein that is able to bind and activate immune inhibitory receptor Pilrα. Here we show that Leda-1/Pianp is strain-specifically expressed in lymphoid organs and macrophages of Th2-prone BALB/c mice but not of Th1-prone C57BL/6J mice. LPS stimulation of BALB/c bone marrow-derived macrophages (BMM) and macrophage-like Raw 264.7 cells conversely regulated Leda-1/Pianp and Pilrα expression. Pilrα induction was caused by LPS-mediated transcriptional modulation and increased mRNA expression. On the other hand, the LPS-mediated decline of Leda-1/Pianp expression was the result of proteolytic degradation by matrix metalloproteinases. In summary, these findings demonstrate that counter-regulation of the ligand-receptor pair Leda-1/Pianp and Pilrα is part of the complex innate immune response of macrophages and its genetically determined strain-specific modulation.

Concurrent and lasting effects of emotion regulation on amygdala response in adolescence and young adulthood.

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.

Cognitive reappraisal of emotion: a meta-analysis of human neuroimaging studies.

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.