Efficacy of N-Acetylcysteine on Endometriosis-Related Pain, Size Reduction of Ovarian Endometriomas, and Fertility Outcomes.

BACKGROUND: Endometriosis is a chronic, estrogen-dependent, inflammatory disease, whose pivotal symptoms are dysmenorrhea, dyspareunia, and chronic pelvic pain (CPP). Besides the usual medical treatments, recent evidence suggests there are potential benefits of oral N-acetylcysteine (NAC) on endometriotic lesions and pain. The primary objective of this prospective single-cohort study was to confirm the effectiveness of NAC in reducing endometriosis-related pain and the size of ovarian endometriomas. The secondary objective was to assess if NAC may play a role in improving fertility and reducing the Ca125 serum levels. METHODS: Patients aged between 18-45 years old with a clinical/histological diagnosis of endometriosis and no current hormonal treatment or pregnancy were included in the study. All patients received quarterly oral NAC 600 mg, 3 tablets/day for 3 consecutive days of the week for 3 months. At baseline and after 3 months, dysmenorrhea, dyspareunia and CPP were assessed using the Visual Analog Scale score (VAS), while the size of the endometriomas was estimated through a transvaginal ultrasound. Analgesics (NSAIDs) intake, the serum levels of Ca125 and the desire for pregnancy were also investigated. Finally, the pregnancy rate of patients with reproductive desire was evaluated. RESULTS: One hundred and twenty patients were recruited. The intensity of dysmenorrhea, dyspareunia and CPP significantly improved (p < 0.0001). The use of NSAIDs (p = 0.001), the size of the endometriomas (p < 0.0001) and the serum levels of Ca125 (p < 0.0001) significantly decreased. Among the 52 patients with reproductive desire, 39 successfully achieved pregnancy within 6 months of starting therapy (p = 0.001). CONCLUSIONS: Oral NAC improves endometriosis-related pain and the size of endometriomas. Furthermore, it decreases Ca125 serum levels and may improve fertility in patients with endometriosis.

BOLD activation on the groundside of figures: More suppression of grounds that competed more for figural status.

A fundamental aspect of object detection is assigning a border to one (figure) side but not the other (ground) side. Figures are shaped; grounds appear shapeless near the figure border. Accumulating evidence supports the view that the mechanism of figure assignment is inhibitory competition with the figure perceived on the winning side. Suppression has been observed on the groundside of figure borders. One prediction is that more suppression will be observed when the groundside competes more for figural status. We tested this prediction by assessing BOLD activation on the groundside of two types of stimuli with articulated borders: AEnov and AEfam stimuli. In both stimulus types, multiple image-based priors (symmetry, closure, small area, enclosure by a larger region) favored the inside as the figure. In AEfam but not AEnov stimuli, the figural prior of familiar configuration present on the outside competes for figural status. Observers perceived the insides of both types of stimuli as novel figures and the outsides as shapeless grounds. Previously, we observed lower BOLD activation in early visual areas representing the grounds of AEfam than AEnov stimuli, although unexpectedly, activation was above baseline. With articulated borders, it can be difficult to exclude figure activation from ground ROIs. Here, our ground ROIs better excluded figure activation; we also added straight-edge (SE) control stimuli and increased the sample size. In early visual areas representing the grounds, we observed lower BOLD activation on the groundside of AEfam than AEnov stimuli and below-baseline BOLD activation on the groundside of SE and AEfam stimuli. These results, indicating that greater suppression is applied to groundsides that competed more for figural status but lost the competition, support a Bayesian model of figure assignment in which proto-objects activated at both low and high levels where image features and familiar configurations are represented, respectively, compete for figural status.

The effects of tDCS on object perception: A systematic review and meta-analysis.

Transcranial direct current stimulation (tDCS) is a novel, non-invasive method of modulating brain activity by applying electrical current directly to the scalp. While the effects of tDCS are more established in the clinical setting, its influence on cognition, specifically object perception, is less clear. The goal of this systematic review was to investigate whether object perception can be improved by tDCS, and if so, under what conditions. A literature search was conducted on the following databases: PubMed, ScienceDirect, Google Scholar and PsycInfo. To be included, studies must have employed tDCS on healthy adult populations and included a measure of object perception. A total of 18 articles met inclusion criteria. The results showed that 58% of studies that applied anodal tDCS to the target region observed enhanced object perception. This was particularly the case with frontal stimulation for object detection tasks. A quantitative meta-analysis further confirmed that anodal tDCS improved object perception overall, and specifically, tDCS to frontal sites increased accuracy scores by an average of 8.8%. Although the qualitative synthesis suggested that anodal tDCS to occipital sites, such as the lateral occipital complex, may enhance object recognition, the meta-analysis showed that this effect was not significant within the occipital subgroup. This is the first systematic review and meta-analysis investigating the effects of tDCS on object perception. Although there are inconsistencies in the behavioral and tDCS methodologies employed by these studies, our analysis revealed that tDCS can enhance object perception when targeting frontal brain regions involved in top-down attention.

Cross-modal masked priming of the tritone paradox.

The tritone paradox is a musical illusion consisting of pairs of octave-ambiguous tones that could be heard as ascending or descending in pitch. This study investigated whether perception of the tritone paradox can be unconsciously influenced by a masked visual prime - specifically, a musical notation. In Experiment 1, participants were first given a "neutral" masked prime (an image of an empty music staff) to assess baseline perception. Then, they were presented with a "meaningful" masked prime consisting of two music notes arranged in either an ascending or a descending configuration, depending on their baseline perception. The results showed that the meaningful prime shifted participants' perception of the tritone paradox in the direction indicated by the musical notation. This effect was stronger for musicians than non-musicians. Experiment 2 replicated Experiment 1 and further ascertained that this effect occurred unconsciously and was not due to regression to the mean. Together, the results of this study demonstrate that relevant visual images can unconsciously influence auditory perception under conditions of ambiguity.

High-definition transcranial direct current stimulation of the lateral occipital cortex influences figure-ground perception.

Prior work has shown that the lateral occipital cortex (LO) is involved in recognition of objects and their parts, as well as segregation of that object (or "figure") from its background. No studies, though, have examined how LO's functioning is influenced by non-invasive brain stimulation, particularly during a figure-ground perception task. The present study tested whether high-definition transcranial direct current stimulation (HD-tDCS) to right LO influences the effects of familiarity on figure-ground perception. Following 20 min of offline anodal stimulation (or sham), participants viewed masked stimuli consisting of two regions separated by a vertical border and were asked to report which region they perceived as figure. One region was the "critical" region, which either depicted a portion of a familiar object ("Familiar" stimuli), or a familiar object with its parts rearranged into a novel configuration ("Part-rearranged" stimuli). Previous research using these stimuli has found higher reports of the critical region as figure for Familiar vs. Part-rearranged displays, demonstrating the effect of familiarity on figure assignment. The results of the current study showed that HD-tDCS to right LO significantly influenced this typical behavioral pattern. Specifically, stimulation (vs. sham) increased reports of the critical region as figure for Part-rearranged stimuli, bringing perception of these displays up to the level of the Familiar stimuli. We interpret this finding as evidence that stimulation of right LO increased participants' reliance on the familiarity of the parts in their figure-ground judgements-a finding consistent with and extending previous research showing that LO is indeed sensitive to object parts. This is the first study showing that HD-tDCS to LO can influence the effects of familiarity on figure-ground perception.

Task-Irrelevant Sound Corrects Leftward Spatial Bias in Blindfolded Haptic Placement Task.

We often rely on our sense of vision for understanding the spatial location of objects around us. If vision cannot be used, one must rely on other senses, such as hearing and touch, in order to build spatial representations. Previous work has found evidence of a leftward spatial bias in visual and tactile tasks. In this study, we sought evidence of this leftward bias in a non-visual haptic object location memory task and assessed the influence of a task-irrelevant sound. In Experiment 1, blindfolded right-handed sighted participants used their non-dominant hand to haptically locate an object on the table, then used their dominant hand to place the object back in its original location. During placement, participants either heard nothing (no-sound condition) or a task-irrelevant repeating tone to the left, right, or front of the room. The results showed that participants exhibited a leftward placement bias on no-sound trials. On sound trials, this leftward bias was corrected; placements were faster and more accurate (regardless of the direction of the sound). One explanation for the leftward bias could be that participants were overcompensating their reach with the right hand during placement. Experiment 2 tested this explanation by switching the hands used for exploration and placement, but found similar results as Experiment 1. A third Experiment found evidence supporting the explanation that sound corrects the leftward bias by heightening attention. Together, these findings show that sound, even if task-irrelevant and semantically unrelated, can correct one's tendency to place objects too far to the left.

Transfer of Learning in People Who Are Blind: Enhancement of Spatial-Cognitive Abilities Through Drawing.

INTRODUCTION: This study assessed whether basic spatial-cognitive abilities can be enhanced in people who are blind through transfer of learning from drawing training. METHODS: Near-body spatial-cognitive performance was assessed through the Cognitive Test for the Blind (CTB), which assesses a wide range of basic spatial-cognitive skills. The CTB was administered to 21 participants who are blind in two behavioral testing sessions separated by five days. For participants in the "trained" group, these intervening days were occupied by the Cognitive-Kinesthetic Drawing Training method, during which participants learned how to draw freehand from memory. The "control" participants were not trained. RESULTS: The results showed significantly increased overall CTB performance in the trained but not in the control group, indicating that the drawing training effectively enhanced spatial-cognitive abilities. A three to six month follow-up session with a subset of trained participants suggested that these training-induced spatial-cognitive improvements might persist over time, at least for some tasks. DISCUSSION: These findings demonstrate that learning to draw from memory without vision over just five sessions can lead to enhancement of basic spatial-cognitive abilities beyond the drawing task. This study is the first to examine the transfer of learning of cognitive ability in blind individuals. IMPLICATIONS FOR PRACTITIONERS: This study sheds light on the Cognitive-Kinesthetic Drawing Training as an effective wide-range rehabilitation technique that could be used to enhance basic spatial-cognitive abilities in those who are blind.

Age-Related Changes in Perirhinal Cortex Sensitivity to Configuration and Part Familiarity and Connectivity to Visual Cortex.

The perirhinal cortex (PRC) is a medial temporal lobe (MTL) structure known to be involved in assessing whether an object is familiar (i.e., meaningful) or novel. Recent evidence shows that the PRC is sensitive to the familiarity of both whole object configurations and their parts, and suggests the PRC may modulate part familiarity responses in V2. Here, using functional magnetic resonance imaging (fMRI), we investigated age-related decline in the PRC's sensitivity to part/configuration familiarity and assessed its functional connectivity to visual cortex in young and older adults. Participants categorized peripherally presented silhouettes as familiar ("real-world") or novel. Part/configuration familiarity was manipulated via three silhouette configurations: Familiar (parts/configurations familiar), Control Novel (parts/configurations novel), and Part-Rearranged Novel (parts familiar, configurations novel). "Real-world" judgments were less accurate than "novel" judgments, although accuracy did not differ between age groups. The fMRI data revealed differential neural activity, however: In young adults, a linear pattern of activation was observed in left hemisphere (LH) PRC, with Familiar > Control Novel > Part-Rearranged Novel. Older adults did not show this pattern, indicating age-related decline in the PRC's sensitivity to part/configuration familiarity. A functional connectivity analysis revealed a significant coupling between the PRC and V2 in the LH in young adults only. Older adults showed a linear pattern of activation in the temporopolar cortex (TPC), but no evidence of TPC-V2 connectivity. This is the first study to demonstrate age-related decline in the PRC's representations of part/configuration familiarity and its covariance with visual cortex.

Memory-guided drawing training increases Granger causal influences from the perirhinal cortex to V1 in the blind.

The perirhinal cortex (PRC) is a medial temporal lobe structure that has been implicated in not only visual memory in the sighted, but also tactile memory in the blind (Cacciamani & Likova, 2016). It has been proposed that, in the blind, the PRC may contribute to modulation of tactile memory responses that emerge in low-level "visual" area V1 as a result of training-induced cortical reorganization (Likova, 2012, 2015). While some studies in the sighted have indicated that the PRC is indeed structurally and functionally connected to the visual cortex (Clavagnier, Falchier, & Kennedy, 2004; Peterson, Cacciamani, Barense, & Scalf, 2012), the PRC's direct modulation of V1 is unknown-particularly in those who lack the visual input that typically stimulates this region. In the present study, we tested Likova's PRC modulation hypothesis; specifically, we used fMRI to assess the PRC's Granger causal influence on V1 activation in the blind during a tactile memory task. To do so, we trained congenital and acquired blind participants on a unique memory-guided drawing technique previously shown to result in V1 reorganization towards tactile memory representations (Likova, 2012). The tasks (20s each) included: tactile exploration of raised line drawings of faces and objects, tactile memory retrieval via drawing, and a scribble motor/memory control. FMRI before and after a week of the Cognitive-Kinesthetic training on these tasks revealed a significant increase in PRC-to-V1 Granger causality from pre- to post-training during the memory drawing task, but not during the motor/memory control. This increase in causal connectivity indicates that the training strengthened the top-down modulation of visual cortex from the PRC. This is the first study to demonstrate enhanced directed functional connectivity from the PRC to the visual cortex in the blind, implicating the PRC as a potential source of the reorganization towards tactile representations that occurs in V1 in the blind brain (Likova, 2012).

Tactile Object Familiarity in the Blind Brain Reveals the Supramodal Perceptual-Mnemonic Nature of the Perirhinal Cortex.

This study is the first to investigate the neural underpinnings of tactile object familiarity in the blind during both perception and memory. In the sighted, the perirhinal cortex (PRC) has been implicated in the assessment of visual object familiarity-a crucial everyday task-as evidenced by reduced activation when an object becomes familiar. Here, to examine the PRC's role in tactile object familiarity in the absence of vision, we trained blind participants on a unique memory-guided drawing technique and measured brain activity while they perceptually explored raised-line drawings, drew them from tactile memory, and scribbled (control). Functional magnetic resonance imaging (fMRI) before and after a week of training revealed a significant decrease in PRC activation from pre- to post-training (i.e., from unfamiliar to familiar) during perceptual exploration as well as memory-guided drawing, but not scribbling. This familiarity-based reduction is the first evidence that the PRC represents tactile object familiarity in the blind. Furthermore, the finding of this effect during both tactile perception and tactile memory provides the critical link in establishing the PRC as a structure whose representations are supramodal for both perception and memory.

The Cortical Network for Braille Writing in the Blind.

Fundamental forms of high-order cognition, such as reading and writing, are usually studied in the context of one modality - vision. People without sight, however, use the kinesthetic-based Braille writing, and haptic-based Braille reading. We asked whether the cognitive and motor control mechanisms underlying writing and reading are modality-specific or supramodal. While a number of previous functional Magnetic Resonance Imaging (fMRI) studies have investigated the brain network for Braille reading in the blind, such studies on Braille writing are lacking. Consequently, no comparative network analysis of Braille writing vs. reading exists. Here, we report the first study of Braille writing, and a comparison of the brain organization for Braille writing vs Braille reading. FMRI was conducted in a Siemens 3T Trio scanner. Our custom MRI-compatible drawing/writing lectern was further modified to provide for Braille reading and writing. Each of five paragraphs of novel Braille text describing objects, faces and navigation sequences was read, then reproduced twice by Braille writing from memory, then read a second time. During Braille reading, the haptic-sensing of the Braille letters strongly activated not only the early visual area V1 and V2, but some highly specialized areas, such as the classical visual grapheme area and the Exner motor grapheme area. Braille-writing-from-memory, engaged a significantly more extensive network in dorsal motor, somatosensory/kinesthetic, dorsal parietal and prefrontal cortex. However, in contrast to the largely extended V1 activation in drawing-from-memory in the blind after training (Likova, 2012), Braille writing from memory generated focal activation restricted to the most foveal part of V1, presumably reflecting topographically the focal demands of such a "pin-pricking" task.

Neural evidence for competition-mediated suppression in the perception of a single object.

Multiple objects compete for representation in visual cortex. Competition may also underlie the perception of a single object. Computational models implement object perception as competition between units on opposite sides of a border. The border is assigned to the winning side, which is perceived as an object (or "figure"), whereas the other side is perceived as a shapeless ground. Behavioral experiments suggest that the ground is inhibited to a degree that depends on the extent to which it competed for object status, and that this inhibition is relayed to low-level brain areas. Here, we used fMRI to assess activation for ground regions of task-irrelevant novel silhouettes presented in the left or right visual field (LVF or RVF) while participants performed a difficult task at fixation. Silhouettes were designed so that the insides would win the competition for object status. The outsides (grounds) suggested portions of familiar objects in half of the silhouettes and novel objects in the other half. Because matches to object memories affect the competition, these two types of silhouettes operationalized, respectively, high competition and low competition from the grounds. The results showed that activation corresponding to ground regions was reduced for high- versus low-competition silhouettes in V4, where receptive fields (RFs) are large enough to encompass the familiar objects in the grounds, and in V1/V2, where RFs are much smaller. These results support a theory of object perception involving competition-mediated ground suppression and feedback from higher to lower levels. This pattern of results was observed in the left hemisphere (RVF), but not in the right hemisphere (LVF). One explanation of the lateralized findings is that task-irrelevant silhouettes in the RVF captured attention, allowing us to observe these effects, whereas those in the LVF did not. Experiment 2 provided preliminary behavioral evidence consistent with this possibility.

Semantic access occurs outside of awareness for the ground side of a figure.

Traditional theories of vision assume that figures and grounds are assigned early in processing, with semantics being accessed later and only by figures, not by grounds. We tested this assumption by showing observers novel silhouettes with borders that suggested familiar objects on their ground side. The ground appeared shapeless near the figure's borders; the familiar objects suggested there were not consciously perceived. Participants' task was to categorize words shown immediately after the silhouettes as naming natural versus artificial objects. The words named objects from the same or from a different superordinate category as the familiar objects suggested in the silhouette ground. In Experiment 1, participants categorized words faster when they followed silhouettes suggesting upright familiar objects from the same rather than a different category on their ground sides, whereas no category differences were observed for inverted silhouettes. This is the first study to show unequivocally that, contrary to traditional assumptions, semantics are accessed for objects that might be perceived on the side of a border that will ultimately be perceived as a shapeless ground. Moreover, although the competition for figural status results in suppression of the shape of the losing contender, its semantics are not suppressed. In Experiment 2, we used longer silhouette-to-word stimulus onset asynchronies to test whether semantics would be suppressed later in time, as might occur if semantics were accessed later than shape memories. No evidence of semantic suppression was observed; indeed, semantic activation of the objects suggested on the ground side of a border appeared to be short-lived. Implications for feedforward versus dynamical interactive theories of object perception are discussed.

Spatially rearranged object parts can facilitate perception of intact whole objects.

The familiarity of an object depends on the spatial arrangement of its parts; when the parts are spatially rearranged, they form a novel, unrecognizable configuration. Yet the same collection of parts comprises both the familiar and novel configuration. Is it possible that the collection of familiar parts activates a representation of the intact familiar configuration even when they are spatially rearranged? We presented novel configurations as primes before test displays that assayed effects on figure-ground perception from memories of intact familiar objects. In our test displays, two equal-area regions shared a central border; one region depicted a portion of a familiar object. Previous research with such displays has shown that participants are more likely to perceive the region depicting a familiar object as the figure and the abutting region as its ground when the familiar object is depicted in its upright orientation rather than upside down. The novel primes comprised either the same or a different collection of parts as the familiar object in the test display (part-rearranged and control primes, respectively). We found that participants were more likely to perceive the familiar region as figure in upright vs. inverted displays following part-rearranged primes but not control primes. Thus, priming with a novel configuration comprising the same familiar parts as the upcoming figure-ground display facilitated orientation-dependent effects of object memories on figure assignment. Similar results were obtained when the spatially rearranged collection of parts was suggested on the groundside of the prime's border, suggesting that familiar parts in novel configurations access the representation of their corresponding intact whole object before figure assignment. These data demonstrate that familiar parts access memories of familiar objects even when they are arranged in a novel configuration.

The perirhinal cortex modulates V2 activity in response to the agreement between part familiarity and configuration familiarity.

Research has demonstrated that the perirhinal cortex (PRC) represents complex object-level feature configurations, and participates in familiarity versus novelty discrimination. Barense et al. [(in press) Cerebral Cortex, 22:11, doi:10.1093/cercor/bhr347] postulated that, in addition, the PRC modulates part familiarity responses in lower-level visual areas. We used fMRI to measure activation in the PRC and V2 in response to silhouettes presented peripherally while participants maintained central fixation and performed an object recognition task. There were three types of silhouettes: Familiar Configurations portrayed real-world objects; Part-Rearranged Novel Configurations created by spatially rearranging the parts of the familiar configurations; and Control Novel Configurations in which both the configuration and the ensemble of parts comprising it were novel. For right visual field (RVF) presentation, BOLD responses revealed a significant linear trend in bilateral BA 35 of the PRC (highest activation for Familiar Configurations, lowest for Part-Rearranged Novel Configurations, with Control Novel Configurations in between). For left visual field (LVF) presentation, a significant linear trend was found in a different area (bilateral BA 38, temporal pole) in the opposite direction (Part-Rearranged Novel Configurations highest, Familiar Configurations lowest). These data confirm that the PRC is sensitive to the agreement in familiarity between the configuration level and the part level. As predicted, V2 activation mimicked that of the PRC: for RVF presentation, activity in V2 was significantly higher in the left hemisphere for Familiar Configurations than for Part-Rearranged Novel Configurations, and for LVF presentation, the opposite effect was found in right hemisphere V2. We attribute these patterns in V2 to feedback from the PRC because receptive fields in V2 encompass parts but not configurations. These results reveal two new aspects of PRC function: (1) it is sensitive to the congruency between the familiarity of object configurations and the parts comprising those configurations and (2) it likely modulates familiarity responses in visual area V2.

Competition-strength-dependent ground suppression in figure-ground perception.

Figure-ground segregation is modeled as inhibitory competition between objects that might be perceived on opposite sides of borders. The winner is the figure; the loser is suppressed, and its location is perceived as shapeless ground. Evidence of ground suppression would support inhibitory competition models and would contribute to explaining why grounds are shapeless near borders shared with figures, yet such evidence is scarce. We manipulated whether competition from potential objects on the ground side of figures was high (i.e., portions of familiar objects were potentially present there) or low (novel objects were potentially present). We predicted that greater competition would produce more ground suppression. The results of two experiments in which suppression was assessed via judgments of the orientation of target bars confirmed this prediction; a third experiment showed that ground suppression is short-lived. Our findings support inhibitory competition models of figure assignment, in particular, and models of visual perception entailing feedback, in general.