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Understanding the neural correlates of repetitive retrieval of emotional events is critical in addressing pathological emotional processing, as repeated processing is central for a number of different therapeutic interventions. In the current study, single-trial functional brain activity was assessed in key regions implicated in episodic retrieval, including the medial prefrontal cortex (mPFC), anterior hippocampus, posterior hippocampus, and the posteromedial parietal cortex (i.e., posterior cingulate cortex and the precuneus) following repeated retrieval of pleasant and unpleasant autobiographical events. Replicating previous studies, repetition prompted reduced blood-oxygen-level-dependent (BOLD) amplitude in the anterior hippocampus and the mPFC, but not in the posterior hippocampus, due to no functional activity during mental imagery, or in the posteromedial parietal cortex, due to enhanced activation that was sustained across repetitions. Neural activation during pleasant and unpleasant autobiographical retrieval did not differ as a function of repetition, indicating similar processing effects regardless of motivational relevance. Taken together, the hedonic valence of retrieved memories does not affect functional activity associated with repeated retrieval of episodic events, in which the pattern of BOLD amplitude change suggests a dissociation between the hippocampal-prefrontal circuit, which shows repetition suppression, and the posteromedial parietal cortex, which shows sustained activation.

Viewing photographic images that depict affectively engaging events prompts a wide variety of psychophysiological and biological reactions that vary as a function of differences in rated pleasure, arousal and specific scene content. In this chapter, we review these data, and conduct new picture-based reliability analyses (using existing databases) with the goal of assessing the extent to which specific pictures reliably engage emotional reactions across individuals. Permutation analyses randomly selected subgroups of individuals and computed the correlation between mean emotional reactivity scores across scenes, resulting in a distribution of correlations for each measure indexing scene reliability. Emotional reactivity scores are compared for different scene contents, and the proportion of exemplars in each content category assessed for strong emotional engagement. For all measures, the data suggest that individual pictures are highly reliable in engaging emotional reactions, and that the specific content that engages the most emotional reactivity varies with measure. These preliminary analyses encourage future investigations aimed at constructing normative biological image databases that, in addition to evaluative reports, provide estimates of emotional reactions in body and brain for use in studies of emotion and emotional dysfunction.

AML SCT-BFM 2007 was the first hematopoietic stem cell transplantation (HCT) trial in Germany to comply with the European Clinical Trials Directive, and aimed to standardize pediatric HCT for acute myeloid leukemia (AML) across centers in Germany, Austria, and the Czech Republic. Children with high-risk features and a good early response achieving a complete first remission (CR-1) and those in CR-2 after a first relapse were stratified to receive HCT from a matched donor after myeloablative conditioning consisting of busulfan, cyclophosphamide, and melphalan. Four-year EFS and OS were 61 and 70%. Cumulative incidence of relapse (CIR) was 22%. TRM was 15% and correlated with age reaching 9% (SE 3%) in children younger than 12 years and 31% (SE 9%) in older children and adolescents. Children with poorly responding primary disease or relapse were allocated to receive early HCT after a cytoreductive regimen with fludarabine, amsacrine, and cytarabine, followed by reduced intensity conditioning and prophylactic donor lymphocyte infusions. Four-year EFS and OS were 49 and 53%. CIR was 38% and TRM 11%. For patients with primary poor response disease, early use of RIC HCT followed by prophylactic DLI can induce long-term remissions in more than 50% (EFS 46% (SE 9%)).

This research examined human defensive reactivity when exposure to an aversive event could be escaped but not entirely avoided. Prolonged visual cues indicated whether exposure to an upcoming aversive (i.e., disgusting) picture could be terminated after onset (escaped) or not, or that a neutral go signal would appear. Acoustically elicited startle reflexes were measured during each cue interval, as were cardiac and skin conductance activity. Early in the cuing interval, startle reflexes were potentiated during both escape and inescapable exposure trials, compared to the simple motor context. Later in the interval, reflexes remained potentiated for both escapable and inescapable trials, with potentiation further enhanced when aversive exposure could not be escaped compared to when exposure could be escaped. Heart rate deceleration in the cuing interval indicated increased vigilance when preparing any (escape or neutral) action, whereas skin conductance responding indicated enhanced sympathetic action mobilization particularly in an escape context. These data suggest that startle reflexes engaged in an escape context reflect both motor-related response inhibition and aversive potentiation, and they indicate that defensive motivation is engaged whenever aversive exposure is guaranteed, regardless of whether it can be escaped or not.

Previous research indicates that predictive cues can dampen subsequent defensive reactions. The present study investigated whether effects of cuing are specific to aversive stimuli, using modulation of the blink startle reflex as a measure of emotional reactivity. Participants viewed pictures depicting violence, romance/ erotica, or mundane content. On half of all trials, a cue (color) predicted the content of the upcoming picture; on the remaining trials, scenes were presented without a cue. Acoustic startle probes were presented during picture viewing on trials with predictive cues and trials without a cue. Replicating previous studies, blink reflexes elicited when viewing violent pictures that had not been preceded by a cue were potentiated compared to un-cued mundane scenes, and reflexes were attenuated when viewing scenes of erotica/ romance that had not been cued. On the other hand, reflex potentiation when viewing scenes of violence (relative to mundane scenes) was eliminated when these pictures were preceded by a predictive cue, whereas scenes of romance prompted reliable reflex attenuation regardless of whether pictures were cued or not. Taken together, the data suggest that cuing elicits an anticipatory coping process that is specific to aversive stimuli.

Evidence is presented supporting a dimension of defensive reactivity that varies across the anxiety disorder spectrum and is defined by physiological responses during threat-imagery challenges that covary with objective measures of psychopathology. Previous imagery studies of anxiety disorders are reviewed, highlighting that, regardless of contemporary diagnostic convention, reliable psychophysiological patterns emerge for patients diagnosed with circumscribed fear compared to those diagnosed with pervasive anxious-misery disorders. Based on the heuristic outlined by the Research Domain Criteria (RDoC) initiative, an exploratory transdiagnostic analysis is presented, based on a sample of 425 treatment-seeking patients from across the spectrum of DSM-IV anxiety diagnoses. Using a composite index of startle reflex and heart rate reactivity during idiographic fear imagery for each patient, a defensive dimension was defined by ranking patients from most defensively reactive to least reactive and then creating five groups of equivalent size (quintile; N = 85). Subsequent analyses showed significant parallel trends of diminishing reactivity in both electrodermal and facial electromyographic reactions across this defensive dimension. Negative affectivity, defined by questionnaire and extent of functional interference, however, showed consistent, inverse trends with defensive reactivity-as reports of distress increased, defensive reactivity was increasingly attenuated. Notably, representatives of each principal diagnosis appeared in each quintile, underscoring the reality of pronounced within-diagnosis heterogeneity in defensive reactivity. In concluding, we describe our new RDoC research project, focusing on the assessment of brain circuit function as it determines hypo/hyperreactivity to challenge-somatic and autonomic-and may relate to patients' stress history and genetic inheritance.

Neural measures of repetition can result in either repetition suppression or enhancement effects, with enhancement sometimes interpreted as indicating episodic retrieval, rather than stimulus habituation. Here, we manipulated whether repetitions were massed (consecutive) or distributed (intermixed) and measured event-related potentials and oscillatory activity, investigating the question of whether there is evidence of "spontaneous" episodic retrieval for distributed, but not massed, repetition. Results showed that distributed repetition uniquely prompted a significant centroparietal old-new effect as well as enhanced theta, compared to either novel presentations or massed repetitions, consistent with a hypothesis of spontaneous retrieval. Massed repetition, on the other hand, prompted repetition suppression and reduction of the N2/P2. Taken together, the data suggest that distributed repetition may facilitate later memory performance because it spontaneously retrieves prior representations.

Repetitions that are distributed (spaced) across time prompt enhancement of a memory-related event-related potential, compared to when repetitions are massed (contiguous). Here, we employed fMRI to investigate neural enhancement and suppression effects during free viewing of natural scenes that were either novel or repeated four times with massed or distributed repetitions. Distributed repetition was uniquely associated with a repetition enhancement effect in a bilateral posterior parietal cluster that included the precuneus and posterior cingulate and which has previously been implicated in episodic memory retrieval. Unique to massed repetition, on the other hand, was enhancement in a right dorsolateral prefrontal cluster that has been implicated in short-term maintenance. Repetition suppression effects for both types of spacing were widespread in regions activated during novel picture processing. Taken together, the data are consistent with a hypothesis that distributed repetition prompts spontaneous retrieval of prior occurrences, whereas massed repetitions prompts short-term maintenance of the episodic representation, due to contiguous presentation. These processing differences may mediate the classic spacing effect in learning and memory.

Background: Typically solid limbal dermoids are excised in pre-school age unless a high irregular astigmatism and its risk for amblyopia lead to an earlier intervention. Case Report: An 80-year-old lady from a rural area complained about a burning, tearing and foreign body sensation of the left eye for two months. In the past two years she had recognized that an extraocular prominence which had been present since birth had shown a tendency to grow. Slit lamp examination showed a markedly prominent and vascularized limbal tumor from 3.30 to 7.00 o'clock. Paralleling the border of the mass there was a bow-shaped stromal lipoid deposit reaching from limbus to limbus. Gonioscopic examination revealed a deep penetration of the process almost into the anterior chamber. The tumor was excised and some fatty tissue adjacent to Descemet's membrane was left. Histological assessment brought us to the diagnosis of a chronically irritated, predescemetal limbal dermoid with marked secondary vascularization, epidermalization, elastoid degeneration and degenerative arcus lipoides. Conclusions: The excision of the limbal dermoid in the described case was performed in the later stage of life. When indicated cosmetically or medically, surgery should typically take place in pre-school age and be performed as a lamellar excision.

Purpose: This case report shows the long-term results after perforating corneo-scleroplasty in a rare case of superior pellucid marginal corneal degeneration with acute hydrops due to rupture of Descemet's membrane. Patient: In the left cornea of a 20-year-old patient with peripheral stromal thinning from 9 to 3 o'clock a rupture in Descemet's membrane occurred followed by lamellar splitting of the mid-stromal region. Due to the decrease in visual acuity and pain from corneal edema a surgical treatment was performed consisting of a perforating/lamellar corneo-scleroplasty protecting the anterior chamber angle. Results: The status has remaind stable for 17 years after surgery with nearly clear graft, best corrected visual acuity of 0.8 and no signs of recurrence or progression of the disease. Central astigmatism is regular, the endothelial cell count is 1250/mm 2 in the central cornea, the central corneal thickness is 540 μm and only a mild vascularised superficial pannus and slight opacities in the predescemetal layer of the graft are found. There are no anterior synechia. On the right eye visual acuity is 0.8 due to slight amblyopia. There are no corneal changes which would indicate bilaterality of the disease. Conclusions: Our findings must be interpreted as an atypically localised superior pellucid marginal corneal degeneration with rupture of Descemet's membrane followed by acute corneal hydrops. When reduction of visual acuity or pain occurs a surgical treatment by perforating/lamellar corneo-scleroplasty can be performed stopping the progression of the disease and achieving a stable optical rehabilitation and absence of pain even after decades.

Recent studies have suggested that pupil diameter, like the "old-new" ERP, may be a measure of memory. Because the amplitude of the old-new ERP is enhanced for items encoded in the context of repetitions that are distributed (spaced), compared to massed (contiguous), we investigated whether pupil diameter is similarly sensitive to repetition. Emotional and neutral pictures of natural scenes were viewed once or repeated with massed (contiguous) or distributed (spaced) repetition during incidental free viewing and then tested on an explicit recognition test. Although an old-new difference in pupil diameter was found during successful recognition, pupil diameter was not enhanced for distributed, compared to massed, repetitions during either recognition or initial free viewing. Moreover, whereas a significant old-new difference was found for erotic scenes that had been seen only once during encoding, this difference was absent when erotic scenes were repeated. Taken together, the data suggest that pupil diameter is not a straightforward index of prior occurrence for natural scenes.

Mental imagery is a fundamental cognitive process of interest to basic scientists and clinical researchers. This study examined large-scale oscillatory brain activity in the alpha band (8-12 Hz) during language-driven mental imagery using dense-array EEG. Three experiments demonstrated relative increases in alpha amplitude: (1) during imagery prompted by words compared to fixation without imagery instruction, (2) during imagery of word content compared to imagery of geometric shapes, and (3) during imagery of emotionally evocative words compared to imagery of less emotionally arousing content. Alpha increases for semantically loaded imagery were observed in parieto-occipital regions, sustained throughout the imagery period. Findings imply that alpha oscillations index active memory and internal cognitive processing, reflecting neural communication in cortical networks representing motor, semantic, and perceptual aspects of the imagined scene.

Cues that signal the possibility of receiving an electric shock reliably induce defensive activation. To determine whether cues can also easily reverse defensive reactions, a threat reversal paradigm was developed in which a cue signaling threat of shock reversed its meaning across the course of the study. This allowed us to contrast defensive reactions to threat cues that became safe cues, with responses to cues that continued to signal threat or safety. Results showed that, when participants were instructed that a previously threatening cue now signaled safety, there was an immediate and complete attenuation of defensive reactions compared to threat cues that maintained their meaning. These findings highlight the role that language can play both in instantiating and attenuating defensive reactions, with implications for understanding emotion regulation, social communication, and clinical phenomena.

A study was carried out to evaluate whether parapapillary atrophy varies among different chronic open-angle glaucomas.The study included 625 Caucasian patients with primary open-angle glaucoma (POAG), 123 patients with secondary open-angle glaucoma (pseudoexfoliative glaucoma n=86; pigmentary glaucoma n=37), and 481 normal subjects. POAG was differentiated into highly myopic POAG (n=32), juvenile POAG (n=33), focal normal-pressure glaucoma (n=46), "sclerotic POAG" with marked fundus tesselation (n=89), and "ordinary POAG" comprising the remaining POAG eyes (n=425). Color stereo optic disc photographs were morphometrically evaluated.The beta zone of parapapillary atrophy was significantly larger in sclerotic POAG (1.00+/-1.37 mm(2)) than in pseudoexfoliative glaucoma (0.65+/-0.93 mm(2)), pigmentary glaucoma (0.42+/-0.58 mm(2)), ordinary POAG (0.66+/-1.06 mm(2)), and focal normal-pressure glaucoma (0.34+/-0.36 mm(2)). In ordinary POAG, the beta zone was significantly larger than in juvenile POAG (0.33+/-0.72 mm(2)). Compared with all glaucoma groups, the beta zone was significantly the smallest in the normal eyes (0. 18+/-0.57 mm(2)). The alpha zone of parapapillary atrophy was significantly larger in the glaucoma groups than in the normal control group, with no significant difference between the glaucoma groups. The myopic crescent (4.11+/-3.42 mm(2)) present in the highly myopic eyes was significantly larger than the beta zone in any other group.The beta zone of parapapillary atrophy varies by a factor of more than 3 between the various types of chronic primary and secondary open-angle glaucomas. This may be important diagnostically and pathogenetically.

An initial reflexive constriction of the pupil to stimulation-the light reflex-is primarily modulated by brightness, but is attenuated when participants are under threat of shock (i.e., fear-inhibited light reflex). The present study assessed whether the light reflex is similarly attenuated when viewing emotional pictures. Pupil diameter was recorded while participants viewed erotic, violent, and neutral scenes that were matched in brightness; scrambled versions identical in brightness were also presented as an additional control. Compared to viewing neutral scenes, the light reflex was reliably modulated by hedonic content, with significant attenuation both when viewing unpleasant as well as pleasant pictures. No differences in the light reflex were found among scrambled versions. Thus, emotional modulation of the initial light reflex is not confined to a context of fear and is not indicative of brightness differences when viewing pictures of natural scenes.

Effects of massed repetition on the modulation of the late positive potential elicited during affective picture viewing were investigated in two experiments. Despite a difference in the number of repetitions across studies (from 5 to 30), results were quite similar: The late positive potential continued to be enhanced when participants viewed emotional, compared to neutral, pictures. On the other hand, massed repetition did prompt a reduction in the late positive potential that was most pronounced for emotional pictures. Startle probe P3 amplitude generally increased with repetition, suggesting diminished attention allocation to repeated pictures. The blink reflex, however, continued to be modulated by hedonic valence, despite massive massed repetition. Taken together, the data suggest that the amplitude of the late positive potential during picture viewing reflects both motivational significance and attention allocation.

Viewing a series of aversive pictures prompts emotional reactivity reflecting sustained defensive engagement. The present study examined the effects of a concurrent visual task on autonomic, somatic, electrocortical, and facial components of this defensive state. Results indicated that emotional activation was largely preserved despite continuous visual distraction, although evidence of attenuation was observed in startle reflex and electrocortical measures. Concurrent task-specific reactivity was also apparent, suggesting that motivational circuits can be simultaneously activated by stimuli with intrinsic survival significance and instructed task significance and that these processes interact differently across the separate components of defensive engagement.

This analysis postulates a motivational continuity from reflex reactions to complex, cognitively elaborated emotional expressions. Responses are motivated by either the positive-appetitive or the negative-aversive brain systems. Reflexes evoked during emotional processing are augmented if their affective valence (positive or negative) matches that of the active motivational system and inhibited when a mismatch is present. Research testing this biphasic model is described using the defensive startle probe reflex. It is shown that probe responses are reliably potentiated during perception and imagery of unpleasant events and reduced during pleasant events. The neurobehavioral foundations of this conception are presented, and the implications of probe analysis are elucidated for theories of emotion organization, the assessment of mood, and practical applications in psychopathology and neurological disorder.

It has been proposed that narrative emotional imagery activates an associative network of stimulus, semantic, and response (procedural) information. In previous research, predicted response components have been demonstrated through psychophysiological methods in peripheral nervous system. Here we investigate central nervous system concomitants of pleasant, neutral, and unpleasant narrative imagery with functional magnetic resonance imaging. Subjects were presented with brief narrative scripts over headphones, and then imagined themselves engaged in the described events. During script perception, auditory association cortex showed enhanced activation during affectively arousing (pleasant and unpleasant), relative to neutral imagery. Structures involved in language processing (left middle frontal gyrus) and spatial navigation (retrosplenium) were also active during script presentation. At the onset of narrative imagery, supplementary motor area, lateral cerebellum, and left inferior frontal gyrus were initiated, showing enhanced signal change during affectively arousing (pleasant and unpleasant), relative to neutral scripts. These data are consistent with a bioinformational model of emotion that considers response mobilization as the measurable output of narrative imagery.

This case report shows the long-term results after perforating corneo-scleroplasty in a rare case of superior pellucid marginal corneal degeneration with acute hydrops due to rupture of Descemet's membrane.In the left cornea of a 20-year-old patient with peripheral stromal thinning from 9 to 3 o'clock a rupture in Descemet's membrane occurred followed by lamellar splitting of the mid-stromal region. Due to the decrease in visual acuity and pain from corneal edema a surgical treatment was performed consisting of a perforating/lamellar corneo-scleroplasty protecting the anterior chamber angle.The status has remained stable for 17 years after surgery with nearly clear graft, best corrected visual acuity of 0.8 and no signs of recurrence or progression of the disease. Central astigmatism is regular, the endothelial cell count is 1250/mm2 in the central cornea, the central corneal thickness is 540 microm and only a mild vascularised superficial pannus and slight opacities in the predescemetal layer of the graft are found. There are no anterior synechia. On the right eye visual acuity is 0.8 due to slight amblyopia. There are no corneal changes which would indicate bilaterality of the disease.Our findings must be interpreted as an atypically localised superior pellucid marginal corneal degeneration with rupture of Descemet's membrane followed by acute corneal hydrops. When reduction of visual acuity or pain occurs a surgical treatment by perforating/lamellar corneo-scleroplasty can be performed stopping the progression of the disease and achieving a stable optical rehabilitation and absence of pain even after decades.