Strong interactions through the highly polar "Early-Late" metal-metal bonds enable single-atom catalysts good durability and superior bifunctional ORR/OER activity.

Simultaneously enhancing the durability and catalytic performance of metal-nitrogen-carbon (M-Nx-C) single-atom catalysts is critical to boost oxygen electrocatalysis for energy conversion and storage, yet it remains a grand challenge. Herein, through the combination of early and late metals, we proposed to enhance the stability and tune the catalytic activity of M-Nx-C SACs in oxygen electrocatalysis by their strong interaction with the M2'C-type MXene substrate. Our density functional theory (DFT) computations revealed that the strong interaction between "early-late" metal-metal bonds significantly improves thermal and electrochemical stability. Due to considerable charge transfer and shift of the d-band center, the electronic properties of these SACs can be extensively modified, thereby optimizing their adsorption strength with oxygenated intermediates and achieving eight promising bifunctional catalysts for ORR/OER with low overpotentials. More importantly, the constant-potential analysis demonstrated the excellent bifunctional activity of SACs supported on MXene substrate across a broad pH range, especially in strongly alkaline media with record-low overpotentials. Further machine learning analysis shows that the d-band center, the charge of the active site, and the work function of the formed heterojunctions are critical to revealing the ORR/OER activity origin. Our results underscore the vast potential of strong interactions between different metal species in enhancing the durability and catalytic performance of SACs.

Efficacy and safety of tepotinib in Asian patients with advanced NSCLC with MET exon 14 skipping enrolled in VISION.

BACKGROUND: Tepotinib, a MET inhibitor approved for the treatment of MET exon 14 (METex14) skipping NSCLC, demonstrated durable clinical activity in VISION (Cohort A + C; N = 313): objective response rate (ORR) 51.4% (95% CI: 45.8, 57.1); median duration of response (mDOR) 18.0 months (95% CI: 12.4, 46.4). We report outcomes in Asian patients from VISION (Cohort A + C) (cut-off: November 20, 2022). METHODS: Patients with advanced METex14 skipping NSCLC, detected by liquid or tissue biopsy, received tepotinib 500 mg (450 mg active moiety) once daily. PRIMARY ENDPOINT: objective response (RECIST 1.1) by independent review. Secondary endpoints included: DOR, progression-free survival (PFS), overall survival (OS), safety, and health-related quality of life (HRQoL). RESULTS: Across treatment lines in 106 Asian patients (39.6% female, 43.4% smoking history, 79.2% adenocarcinoma, 47.2% treatment-naive), ORR was 56.6% (95% CI: 46.6, 66.2), mDOR 18.5 months (10.4, ne), mPFS 13.8 months (10.8, 22.0), and mOS 25.5 months (19.3, 36.4). Consistent efficacy observed, regardless of baseline characteristics. HRQoL remained stable during treatment. Treatment-related adverse events (TRAEs) occurred in 95.3% of patients (39.6% Grade ≥3). Most common TRAEs: peripheral edema (62.3%), creatinine increase (38.7%). CONCLUSIONS: Tepotinib demonstrated robust and durable efficacy, with a manageable safety profile, in Asian patients with METex14 skipping NSCLC. CLINICAL TRIAL REGISTRATION: NCT02864992.

Genome Size in the Arenaria ciliata Species Complex (Caryophyllaceae), with Special Focus on Northern Europe and the Arctic.

The main aim of the present study has been the completion of genome size data for the diverse arctic-alpine A. ciliata species complex, with special focus on the unexplored arctic taxon A. pseudofrigida, the north-European A. norvegica, and A. gothica from Gotland (Sweden). Altogether, 46 individuals of these three Nordic taxa have been sampled from seven different regions and their genome size estimated using flow cytometry. Three other alpine taxa in the A. ciliata complex (A. multicaulis, A. ciliata subsp. ciliata, and A. ciliata subsp. bernensis) were also collected and analyzed for standardization purposes, comprising 20 individuals from six regions. A mean 2c value of 1.65 pg of DNA was recorded for A. pseudofrigida, 2.80 pg for A. norvegica, and 4.14 pg for A. gothica, as against the reconfirmed 2c value of 1.63 pg DNA for the type taxon A. ciliata subsp. ciliata. Our results presenting the first estimations of genome sizes for the newly sampled taxa, corroborate ploidy levels described in the available literature, with A. pseudofrigida being tetraploid (2n = 4x = 40), A. norvegica possessing predominantly 2n = 8x = 80, and A. gothica with 2n = 10x = 100. The present study also reconfirms genome size and ploidy level estimations published previously for the alpine members of this species complex. Reflecting a likely complex recent biogeographic history, the A. ciliata species group comprises a polyploid arctic-alpine species complex characterized by reticulate evolution, polyploidizations and hybridizations, probably associated with rapid latitudinal and altitudinal migrations in the Pleistocene-Holocene period.

"Show me how to use a microscope" - The development and evaluation of certification as direct assessment of practical lab skills.

Practical lab skills are rarely directly assessed. To improve constructive alignment between the described learning outcomes of practical skills and assessment, we developed and tested a certification procedure for microscopy skills. The procedure was embedded into the ordinary learning activity, so no additional time was needed. Three slightly different protocols were developed within the framework of sociocultural learning theory and built like a skill ladder, including direct peer assessment and elements of gamified learning. The protocols varied slightly in the way students were prepared for the certification, the number of steps/levels of achievement, and the consequences of failing. We tested the protocols at three different academic institutions and within 11 courses of varying sizes and academic levels in biology or geology. Feedbacks were collected through online surveys (n = 207) or orally after sessions. One protocol provided instruction videos as preparation material. Instruction videos provided increased understanding of the task, but tactile training was most important for learning. Regardless of institution, type of preparation, and level of former experience, the certification procedure made students clearly more engaged in the exercise. The majority reported that the certification procedure increased their motivation to learn, increased their perceived learning outcome, and was appropriate for assessing practical skills. Students with no or little experience in microscopy before the exercise were more positive about the certification procedure compared to skilled students, and the level of engagement and preparation was higher when there were some consequences of failing. Most students felt comfortable being certified by peers, but some students expressed concern about peers making mistakes. The presented certification procedure can easily be adapted to assess other practical skills and, with some adjustments, be an efficient method for assessment-as-learning, merging formative- and summative assessment.

Interactions between winter temperatures and duration of exposure may structure Arctic microarthropod communities.

The Arctic has a diverse terrestrial microarthropod fauna which overwinters in situ in soil and vegetation. This fauna is involved in key ecosystem processes, for example decomposition and pollination, and has tolerance to the Arctic's winter conditions. However, the Arctic is undergoing rapid change. Svalbard is experiencing warming rates up to four times the global average as well as alterations in precipitation (quantity and form; snow or rain) and wind direction. These will modify the conditions experienced by the overwintering fauna. Since laboratory experiments often fail to capture the diversity of environmental stressors, we employed a manipulation experiment using the naturally accumulating snow pack to moderate soil winter soil temperatures, combined with an extended incubator treatment, to map the duration limits of naturally induced cold tolerance. We demonstrate that the Collembola fauna can tolerate temperatures of -25 °C but that, in areas devoid of snow accumulation and when soil temperatures dip below -30 °C there is significant mortality. Furthermore, we demonstrate that exposure to a further extended 12 month period at -6 °C, as a simple model of a situation where snow cover is not lost during the short Arctic summer, results in additional mortality with relatively few Collembola surviving. By contrast, while oribatid mites displayed similar survival over a natural winter as the Collembola, they were highly resistant to the extended exposure at -6 °C, with no additional mortality occurring. We also documented survival amongst other invertebrate groups, including Nematocera and Brachycera larvae, Hemiptera (Acyrthosiphon svalbardicum), Coleoptera (Isochnus flagellum), and Araneae (Linyphiidae). We conclude that snow depth and winter air temperatures interact to regulate soil microarthropod populations over local scales and therefore the functioning of the Arctic soil ecosystem. Moreover, the environmental changes currently being observed in polar regions will continue to modify this fauna and its local and micro-scale distribution.

In chronic complete spinal cord injury supraspinal changes detected by quantitative MRI are confined to volume reduction in the caudal brainstem.

There is much controversy about the potential impact of spinal cord injury (SCI) on brain anatomy and function, which is mirrored in the substantial divergence of findings between animal models and human imaging studies. Given recent advances in quantitative magnetic resonance imaging (MRI) we sought to tackle the unresolved question about the link between the presumed injury associated volume differences and underlying brain tissue property changes in a cohort of chronic complete SCI patients. Using the established computational anatomy methods of voxel-based morphometry (VBM) and voxel-based quantification (VBQ), we performed statistical analyses on grey and white matter volumes as well as on parameter maps indicative for myelin, iron, and free tissue water content in the brain of complete SCI patients (n = 14) and healthy individuals (n = 14). Our regionally unbiased white matter analysis showed a significant volume reduction of the dorsal aspect at the junction between the most rostral part of the spinal cord and the medulla oblongata consistent with Wallerian degeneration of proprioceptive axons in the dorsal column tracts in SCI subjects. This observation strongly correlated with spinal cord atrophy assessed by quantification of the spinal cord cross-sectional area at the cervical level C2/3. These findings suggest that Wallerian degeneration of the dorsal column tracts represents a main contributor to the observed spinal cord atrophy, which is highly consistent with preclinical histological evidence of remote changes in the central nervous system secondary to SCI. Structural changes in other brain regions representing remote changes in the course of chronic SCI could neither be confirmed by conventional VBM nor by VBQ analysis. Whether and how MRI based brain morphometry and brain tissue property analysis will inform clinical decision making and clinical trial outcomes in spinal cord medicine remains to be determined.

Spatial characteristics of spontaneous and stimulus-induced individual functional connectivity networks in severe disorders of consciousness.

BACKGROUND: Functional connectivity (fcMRI) analyses of resting state functional magnetic resonance imaging (fMRI) data revealed substantial differences between states of consciousness. The underlying cause-effect linkage, however, remains unknown to the present day. The aim of this study was to examine the relationship between fcMRI measures and Disorders of Consciousness (DOC) in resting state and under adequate stimulation. METHODS AND FINDINGS: fMRI data from thirteen patients with unresponsive wakefulness syndrome, eight patients in minimally conscious state, and eleven healthy controls were acquired in rest and during the application of nociceptive and emotional acoustic stimuli. We compared spatial characteristics and anatomical topography of seed-based fcMRI networks on group and individual levels. The anatomical topography of fcMRI networks of patients was altered in all three conditions as compared with healthy controls. Spread and distribution of individual fcMRI networks, however, differed significantly between patients and healthy controls in stimulation conditions only. The exploration of individual metric values identified two patients whose spatial metrics did not deviate from metric distributions of healthy controls in a statistically meaningful manner. CONCLUSIONS: These findings suggest that the disturbance of consciousness in DOC is related to deficits in global topographical network organization rather than a principal inability to establish long-distance connections. In addition, the results question the claim that task-free measurements are particularly valuable as a tool for individual diagnostics in severe neurological disorders. Further studies comparing connectivity indices with outcome of DOC patients are needed to determine the clinical relevance of spatial metrics and stimulation paradigms for individual diagnosis, prognosis and treatment in DOC.

On the relationship between negative affective priming and prefrontal cognitive control mechanisms.

Although several studies have examined inhibition of affective stimuli, valence-dependent cognitive control effects remain poorly understood. Behavioural and functional imaging (functional magnetic resonance imaging) data were collected from 17 healthy participants to examine neural correlates of the Negative Affective Priming (NAP) task. We created relative ratio scores considering the reaction times of prime trials in order to assess the amount of interference after the presentation of negative and positive distracter words. Behavioural results showed an attenuated NAP effect for negative distracters compared to neutral stimuli. Furthermore, priming negative distracters generated more interference by reacting to the probe target than positive distracters. Neuroimaging data revealed a stronger prefrontal activation during negative NAP trials compared to positive NAP and neutral control trials, which was reflected in a heightened activation of superior and middle frontal gyrus as well as parietal cortex. The findings show the impact of negative distracters on prefrontal response, contributing to the understanding of NAP effects in healthy subjects.

Behavioral and central correlates of contextual fear learning and contextual modulation of cued fear in posttraumatic stress disorder.

Patients with posttraumatic stress disorder (PTSD) show persistent fear responses to trauma cues in contexts in which these cues no longer predict danger. This might be related to deficient context and enhanced cue conditioning. To test this hypothesis, we examined context conditioning directly followed by a cue conditioning phase against the background of the previously conditioned context in 12 patients with PTSD, 14 traumatized control subjects without PTSD and 11 matched never-traumatized controls. We used differential context and cue conditioning paradigms, with rooms as contexts and geometric figures as cues, and assessed valence, arousal and contingency ratings as well as brain responses using functional magnetic resonance imaging. The PTSD patients showed more hippocampal activation and differentiated the threat and safe contexts less in their contingency ratings than the healthy controls during context acquisition. In the subsequent cue acquisition against the background of the conditioned context, they displayed similar threat versus safe cue differentiation in contingency ratings as the two control groups. Moreover, PTSD patients failed to extinguish the differential conditioned context and cued fear responses and showed increased fear to both the dangerous and the safe conditioned contexts and cues in some ratings. This study provides evidence for a dissociation of brain responses and contingency awareness in PTSD which represents impaired context learning and a deficient contextual modulation of cue-related associations. In addition, extinction and extinction recall were impaired in PTSD. These changes were related to PTSD symptoms and suggest that contextual learning deficits may contribute to PTSD.

Mapping nutrient resorption efficiencies of subarctic cryptogams and seed plants onto the Tree of Life.

Nutrient resorption from senescing photosynthetic organs is a powerful mechanism for conserving nitrogen (N) and phosphorus (P) in infertile environments. Evolution has resulted in enhanced differentiation of conducting tissues to facilitate transport of photosynthate to other plant parts, ultimately leading to phloem. Such tissues may also serve to translocate N and P to other plant parts upon their senescence. Therefore, we hypothesize that nutrient resorption efficiency (RE, % of nutrient pool exported) should correspond with the degree of specialization of these conducting tissues across the autotrophic branches of the Tree of Life. To test this hypothesis, we had to compare members of different plant clades and lichens within a climatic region, to minimize confounding effects of climatic drivers on nutrient resorption. Thus, we compared RE among wide-ranging basal clades from the principally N-limited subarctic region, employing a novel method to correct for mass loss during senescence. Even with the limited numbers of species available for certain clades in this region, we found some consistent patterns. Mosses, lichens, and lycophytes generally showed low REN (<20%), liverworts and conifers intermediate (40%) and monilophytes, eudicots, and monocots high (>70%). REP appeared higher in eudicots and liverworts than in mosses. Within mosses, taxa with more efficient conductance also showed higher REN. The differences in REN among clades broadly matched the degree of specialization of conducting tissues. This novel mapping of a physiological process onto the Tree of Life broadly supports the idea that the evolution of conducting tissues toward specialized phloem has aided land plants to optimize their internal nitrogen recycling. The generality of evolutionary lines in conducting tissues and nutrient resorption efficiency needs to be tested across different floras in different climatic regions with different levels of N versus P availability.

Neuroticism developmental courses--implications for depression, anxiety and everyday emotional experience; a prospective study from adolescence to young adulthood.

BACKGROUND: Neuroticism is frequently discussed as a risk factor for psychopathology. According to the maturity principle, neuroticism decreases over the course of life, but not uniformly across individuals. However, the implications of differences in personality maturation on mental health have not been well studied so far. Hence, we hypothesized that different forms of neuroticism development from adolescence to young adulthood are associated with differences in depression, anxiety and everyday emotional experience at the age of 25. METHODS: A sample of 266 adolescents from the general population was examined three times over ten years (age at T0: 15, T1: 20 and T2: 25) using questionnaires, interviews and ecological momentary assessment (EMA). At all measurement points, neuroticism was assessed with the NEO inventory. At T2, diagnoses of major depression and anxiety disorders were captured with a structured clinical interview (M-CIDI). Phone-based EMA was used to assess emotional experience and affective instability over a two-week period at T2. RESULTS: The best fitting model was a latent class growth analysis with two groups of neuroticism development. Most individuals (n = 205) showed moderate values whereas 61 participants were clustered into a group with elevated neuroticism levels. In both groups neuroticism significantly changed during the ten year period with a peak at the age of 20. Individuals with a higher absolute level were at 14-fold increased risk for depression and 7-fold risk for anxiety disorders at the age of 25. In EMA, increased negative affect and arousal as well as decreased positive emotions were found in this high group. CONCLUSIONS: Other than expected, personality did not mature in our sample. However, there was a significant change of neuroticism values from adolescence to young adulthood. Further, over 20% of our participants showed a neuroticism development which was associated with adverse outcomes such as negatively toned emotional experience and a heightened risk to suffer from depressive and anxiety disorders in young adulthood. These high-risk persons need to be identified early to provide interventions supporting continuous personality maturation.

What kind of consciousness is minimal?

PRIMARY OBJECTIVE: A comparison between unitary and non-unitary views on minimal consciousness. RESEARCH DESIGN: First, unitary (all-or-none) and non-unitary (gradual or continuous) models of consciousness are defined as they have been developed in both philosophy and neurophysiology. Then, the implications of these ideas to the notion the minimally conscious state (MCS) are discussed. METHODS AND PROCEDURES: Review and analysis of theoretical conceptions and empirical data. MAIN OUTCOME AND RESULTS: Both kinds of models are compatible with the actual definitions of MCS. Although unitary views may seem to contradict the description of the MCS in 'Neurology' 2002, the apparent contradiction can easily be solved. Most recent data, particularly those obtained using fMRI and concerning learning, emotional responsiveness and pain and suffering, speak for non-unitary models. CONCLUSIONS: Most evidence speaks for non-unitary models of minimal consciousness. If these models are correct, patients with MCS may have, in addition to temporal fluctuations, a lower level of consciousness compared with fully conscious individuals. A still lower level could characterize patients diagnosed as unresponsive wakefulness syndrome (UWS). From this point of view, therefore, the difference between UWS and MCS is gradual rather than qualitative. However, due to methodological limitations of the available studies, the evidence for non-unitary models cannot be regarded as definite.

Detaching from the negative by reappraisal: the role of right superior frontal gyrus (BA9/32).

The ability to reappraise the emotional impact of events is related to long-term mental health. Self-focused reappraisal (REAPPself), i.e., reducing the personal relevance of the negative events, has been previously associated with neural activity in regions near right medial prefrontal cortex, but rarely investigated among brain-damaged individuals. Thus, we aimed to examine the REAPPself ability of brain-damaged patients and healthy controls considering structural atrophies and gray matter intensities, respectively. Twenty patients with well-defined cortex lesions due to an acquired circumscribed tumor or cyst and 23 healthy controls performed a REAPPself task, in which they had to either observe negative stimuli or decrease emotional responding by REAPPself. Next, they rated the impact of negative arousal and valence. REAPPself ability scores were calculated by subtracting the negative picture ratings after applying REAPPself from the ratings of the observing condition. The scores of the patients were included in a voxel-based lesion-symptom mapping (VLSM) analysis to identify deficit related areas (ROI). Then, a ROI group-wise comparison was performed. Additionally, a whole-brain voxel-based-morphometry (VBM) analysis was run, in which healthy participant's REAPPself ability scores were correlated with gray matter intensities. Results showed that (1) regions in the right superior frontal gyrus (SFG), comprising the right dorsolateral prefrontal cortex (BA9) and the right dorsal anterior cingulate cortex (BA32), were associated with patient's impaired down-regulation of arousal, (2) a lesion in the depicted ROI occasioned significant REAPPself impairments, (3) REAPPself ability of controls was linked with increased gray matter intensities in the ROI regions. Our findings show for the first time that the neural integrity and the structural volume of right SFG regions (BA9/32) might be indispensable for REAPPself. Implications for neurofeedback research are discussed.

True or false? Activations of language-related areas in patients with disorders of consciousness.

Twenty-nine patients with Unresponsive Wakefulness Syndrome (UWS), 26 patients in Minimally Conscious State (MCS), and 21 healthy control individuals matched in age and social environment (patients' relatives) were presented with 80 short sentences half of which were factually correct, and the other half factually incorrect. The diagnosis was made on the basis of repeated neurological examinations as well as the standardized assessment using a Coma Recovery Scale-Revised (CRS-R). fMRI blood oxygen level dependent signal was recorded in an event-related design time-locked to the end word of the sentences. In the contrast "incorrect-minus-correct" significant activations in the relevant brain regions were obtained in 17 (81%) controls and in 16 (29%) patients. Among patients, the 16 responders had a significantly longer time since accident than the 39 non-responders. Responders and non-responders did not differ in terms of the diagnosis (UWS vs. MCS), age, CRS-R score, or the degree of brain atrophy. The data concur with the results of several earlier studies on UWS/MCS patients, with the difference that the critical stimuli in those studies were semantically incongruent or ambiguous propositions rather than factually false ones in the present experiment. The hypothesis is discussed that the differential response of brain language areas to factually correct and incorrect statements does not require conscious perception of the statements.

Neural correlates of sensory preconditioning: a preliminary fMRI investigation.

Sensory preconditioning (SPC; also known as behaviorally silent learning) consists of a combination of two neutral stimuli, none of which elicits an unconditional response. After one of them is later paired with an unconditional stimulus (US), the other neutral stimulus also yields a conditional response although it has never been paired with the US. In this study, an event-related functional magnetic resonance imaging (fMRI) paradigm was used to specify brain regions involved in SPC. The results demonstrated that SPC was associated with significant changes in activity of several regions, notably, the left amygdala, the left hippocampus, the bilateral thalamus, the bilateral medial globus pallidus, the bilateral cerebellum, the bilateral premotor cortex, and the bilateral middle frontal gyrus. This is a first effort to use fMRI to examine the effects of SPC on brain activation. Our data suggest that there is a distributed network of structures involved in SPC including both cortical and subcortical regions, therefore add to our understanding of the neural mechanisms underlying the ability to associative learning.

Can mental imagery functional magnetic resonance imaging predict recovery in patients with disorders of consciousness?

OBJECTIVE: To determine the potential prognostic value of using functional magnetic resonance imaging (fMRI) to identify patients with disorders of consciousness, who show potential for recovery. DESIGN: Observational study. SETTING: Unit for acute rehabilitation care. PARTICIPANTS: Patients (N=22) in a vegetative state (VS; n=10) and minimally conscious state (MCS; n=12) during the first 200 days after the initial incident. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Further course on the Coma Recovery Scale-Revised. RESULTS: Participants performed a mental imagery fMRI paradigm. They were asked to alternately imagine playing tennis and navigating through their home. In 14 of the 22 examined patients (VS, n=5; MCS, n=9), a significant activation of the regions of interest (ROIs) of the mental imagery paradigm could be found. All 5 patients with activation of a significant blood oxygen level dependent signal, who were in a VS at the time of the fMRI examination, reached at least an MCS at the end of the observation period. In contrast, 5 participants in a VS who failed to show activation in ROIs, did not (sensitivity 100%, specificity 100%). Six of 9 patients in an MCS with activation in ROIs emerged from an MCS. Of 3 patients in an MCS who did not show activation, 2 patients stayed in an MCS and 1 patient emerged from the MCS (sensitivity 85%, specificity 40%). CONCLUSIONS: The fMRI paradigm mental imagery displays a high concordance with the further clinical course of patients in a VS. All 5 patients in a VS who showed significant activation of ROIs had a favorable further course until the end of the observation period. We therefore propose the term "functional minimally conscious state" for these patients. They may benefit from rehabilitation treatment. In cases where no significant activation was seen, the method has no prognostic value. Prediction of the clinical course of patients in an MCS by fMRI was considerably less accurate than in patients in a VS.

Brain processing of pain in patients with unresponsive wakefulness syndrome.

By definition, patients with unresponsive wakefulness syndrome (UWS) do not experience pain, but it is still not completely understood how far their brain can process noxious stimuli. The few positron emission tomography studies that have examined pain processing did not yield a clear and consistent result. We performed an functional magnetic resonance imaging scan in 30 UWS patients of nontraumatic etiology and 15 age- and sex-matched healthy control participants (HC). In a block design, noxious electrical stimuli were presented at the patients' left index finger, alternating with a resting baseline condition. Sixteen of the UWS patients (53%) showed neural activation in at least one subsystem of the pain-processing network. More specifically, 15 UWS patients (50%) showed responses in the sensory-discriminative pain network, 30% in the affective pain network. The data indicate that some patients completely fulfilling the clinical UWS criteria have the neural substrates of noxious stimulation processing, which resemble that in control individuals. We therefore suppose that at least some of these patients can experience pain.

Patients with unresponsive wakefulness syndrome respond to the pain cries of other people.

OBJECTIVE: Recent publications show that using imagery instructions, brain activation patterns indicating consciousness can be found in approximately 10% of patients with unresponsive wakefulness syndrome (UWS; previously called vegetative state). It is possible, however, that patients who cannot follow instructions (because of limited memory/attention capacities, for example) are nevertheless conscious and retain emotional abilities to feel pain and pleasure. The aim of this study was to assess residual affective consciousness in a specific network of brain structures, the so-called pain matrix (PM) of the brain. METHODS: We examined 44 carefully diagnosed UWS patients at 2 imaging centers. fMRI was used to investigate the brain hemodynamic responses to (a) imagery instructions, and (b) pain cries as opposed to neutral human vocalizations. RESULTS: In line with the data of other groups, consistent responses to imagery instructions were obtained in 5 patients. In contrast, the PM was activated by pain cries in 24 patients. The PM consists of a sensory subsystem, which underlies pain sensation, and an affective subsystem, which underlies the characteristic aversive emotional tone of pain. The former was activated in 34% of patients, the latter in 30% of patients. CONCLUSION: Although there is debate about whether patients with UWS can perceive their own pain, our data indicate that many of them respond to the signals of pain in others. One can speculate that "affective consciousness" can remain even in patients with very severe brain damage who have no capacity for cognition.

Global functional connectivity reveals highly significant differences between the vegetative and the minimally conscious state.

A major challenge in the diagnosis of disorders of consciousness is the differential diagnosis between the vegetative state (VS) and the minimally conscious state (MCS). Clinically, VS is defined by complete unawareness, whereas MCS is defined by the presence of inconsistent but clearly discernible behavioural signs of consciousness. In healthy individuals, pain cries have been reported to elicit functional activation within the pain matrix of the brain, which may be interpreted as empathic reaction. In this study, pain cries were presented to six VS patients, six MCS patients, and 17 age-matched healthy controls. Conventional task-related functional magnetic resonance imaging (fMRI) showed no significant differences in functional activation between the VS and MCS groups. In contrast to this negative finding, the application of a novel data-driven technique for the analysis of the brain's global functional connectivity yielded a positive result. The weighted global connectivity (WGC) was significantly greater in the MCS group compared to the VS group (p < 0.05, family-wise error corrected). Using areas of significant WGC differences as 'seed regions' in a secondary connectivity analysis revealed extended functional networks in both MCS and healthy groups, whereas no such long-range functional connections were observed in the VS group. These results demonstrate the potential of functional connectivity MRI (fcMRI) as a clinical tool for differential diagnosis in disorders of consciousness.

Hypersensitivity in borderline personality disorder during mindreading.

BACKGROUND: One of the core symptoms of borderline personality disorder (BPD) is the instability in interpersonal relationships. This might be related to existent differences in mindreading between BPD patients and healthy individuals. METHODS: We examined the behavioural and neurophysiological (fMRI) responses of BPD patients and healthy controls (HC) during performance of the 'Reading the Mind in the Eyes' test (RMET). RESULTS: Mental state discrimination was significantly better and faster for affective eye gazes in BPD patients than in HC. At the neurophysiological level, this was manifested in a stronger activation of the amygdala and greater activity of the medial frontal gyrus, the left temporal pole and the middle temporal gyrus during affective eye gazes. In contrast, HC subjects showed a greater activation in the insula and the superior temporal gyri. CONCLUSION: These findings indicate that BPD patients are highly vigilant to social stimuli, maybe because they resonate intuitively with mental states of others.