Tal Golan

Allicin Purified From Fresh Garlic Cloves Induces Apoptosis in Colon Cancer Cells Via Nrf2

Allicin (diallyl thiosulfinate) is the best-known biologically active component in freshly crushed garlic extract. We developed a novel, simple method to isolate active allicin, which yielded a stable compound in aqueous solution amenable for use in in vitro and in vivo studies. We focused on the in vitro effects of allicin on cell proliferation of colon cancer cell lines HCT-116, LS174T, HT-29, and Caco-2 and assessed the underlying mechanisms. This allicin preparation exerted a time- and dose-dependent cytostatic effect on these cells at concentrations ranging from 6.2 to 310 μM. Treatment with allicin resulted in HCT-116 apoptotic cell death as demonstrated by enhanced hypodiploid DNA content, decreased levels of B-cell non-Hodgkin lymphoma-2 (Bcl-2), increased levels of bax and increased capability of releasing cytochrome c from mitochondria to the cytosol. Allicin also induced translocation of NF-E2-related factor-2 (Nrf2) to the nuclei of HCT-116 cells. Luciferase reporter gene assay showed that allicin induces Nrf2-mediated luciferase transactivation activity. SiRNA knock down of Nrf2 significantly affected the capacity of allicin to inhibit HCT-116 proliferation. These results suggest that Nrf2 mediates the allicin-induced apoptotic death of colon cancer cells.

The wide window of face detection

Faces are detected more rapidly than other objects in visual scenes and search arrays, but the cause for this face advantage has been contested. In the present study, we found that under conditions of spatial uncertainty, faces were easier to detect than control targets (dog faces, clocks and cars) even in the absence of surrounding stimuli, making an explanation based only on low-level differences unlikely. This advantage improved with eccentricity in the visual field, enabling face detection in wider visual windows, and pointing to selective sparing of face detection at greater eccentricities. This face advantage might be due to perceptual factors favoring face detection. In addition, the relative face advantage is greater under flanked than non-flanked conditions, suggesting an additional, possibly attention-related benefit enabling face detection in groups of distracters.

Human face preference in Gamma-Frequency EEG activity

Previous studies demonstrated that induced EEG activity in the gamma band (iGBA) plays an important role in object recognition and is modulated by stimulus familiarity and its compatibility with pre-existent representations. In the present study we investigated the modulation of iGBA by the degree of familiarity and perceptual expertise that observers have with stimuli from different categories. Specifically, we compared iGBA in response to human faces versus stimuli which subjects are not expert with (ape faces, human hands, buildings and watches). iGBA elicited by human faces was higher and peaked earlier than that elicited by all other categories, which did not differ significantly from each other. These findings can be accounted for by two characteristics of perceptual expertise. One is the activation of a richer, stronger and, therefore, more easily accessible mental representation of human faces. The second is the more detailed perceptual processing necessary for within-category distinctions, which is the hallmark of perceptual expertise. In addition, the sensitivity of iGBA to human but not ape faces was contrasted with the face-sensitive N170-effect, which was similar for human and ape faces. In concert with previous studies, this dissociation suggests a multi-level neuronal model of face recognition, manifested by these two electrophysiological measures, discussed in this paper.

Association and dissociation between detection and discrimination of objects of expertise: Evidence from visual search

Expertise in face recognition is characterized by high proficiency in distinguishing between individual faces. However, faces also enjoy an advantage at the early stage of basic-level detection, as demonstrated by efficient visual search for faces among nonface objects. In the present study, we asked (1) whether the face advantage in detection is a unique signature of face expertise, or whether it generalizes to other objects of expertise, and (2) whether expertise in face detection is intrinsically linked to expertise in face individuation. We compared how groups with varying degrees of object and face expertise (typical adults, developmental prosopagnosics [DP], and car experts) search for objects within and outside their domains of expertise (faces, cars, airplanes, and butterflies) among a variable set of object distractors. Across all three groups, search efficiency (indexed by reaction time slopes) was higher for faces and airplanes than for cars and butterflies. Notably, the search slope for car targets was considerably shallower in the car experts than in nonexperts. Although the mean face slope was slightly steeper among the DPs than in the other two groups, most of the DPs’ search slopes were well within the normative range. This pattern of results suggests that expertise in object detection is indeed associated with expertise at the subordinate level, that it is not specific to faces, and that the two types of expertise are distinct facilities. We discuss the potential role of experience in bridging between low-level discriminative features and high-level naturalistic categories.

Spontaneously Emerging Patterns in Human Visual Cortex Reflect Responses to Naturalistic Sensory Stimuli

Abstract In the absence of stimulus or task, the cortex spontaneously generates rich and consistent functional connectivity patterns (termed resting state networks) which are evident even within individual cortical areas. We and others have previously hypothesized that habitual cortical network activations during daily life contribute to the shaping of these connectivity patterns. Here we tested this hypothesis by comparing, using blood oxygen level‐dependent‐functional magnetic resonance imaging, the connectivity patterns that spontaneously emerge during rest in retinotopic visual areas to the patterns generated by naturalistic visual stimuli (repeated movie segments). These were then compared with connectivity patterns produced by more standard retinotopic mapping stimuli (polar and eccentricity mapping). Our results reveal that the movie‐driven patterns were significantly more similar to the spontaneously emerging patterns, compared with the connectivity patterns of either eccentricity or polar mapping stimuli. Intentional visual imagery of naturalistic stimuli was unlikely to underlie these results, since they were duplicated when participants were engaged in an auditory task. Our results suggest that the connectivity patterns that appear during rest better reflect naturalistic activations rather than controlled, artificially designed stimuli. The results are compatible with the hypothesis that the spontaneous connectivity patterns in human retinotopic areas reflect the statistics of cortical coactivations during natural vision.

Intracranial recordings reveal transient response dynamics during information maintenance in human cerebral cortex

Despite an extensive body of work, it is still not clear how short term maintenance of information is implemented in the human brain. Most prior research has focused on “working memory”—typically involving the storage of a number of items, requiring the use of a phonological loop and focused attention during the delay period between encoding and retrieval. These studies largely support a model of enhanced activity in the delay interval as the central mechanism underlying working memory. However, multi‐item working memory constitutes only a subset of storage phenomena that may occur during daily life. A common task in naturalistic situations is short term memory of a single item—for example, blindly reaching to a previously placed cup of coffee. Little is known about such single‐item, effortless, storage in the human brain. Here, we examined the dynamics of brain responses during a single‐item maintenance task, using intracranial recordings implanted for clinical purpose in patients (ECoG). Our results reveal that active electrodes were dominated by transient short latency visual and motor responses, reflected in broadband high frequency power increases in occipito‐temporal, frontal, and parietal cortex. Only a very small set of electrodes showed activity during the early part of the delay period. Interestingly, no cortical site displayed a significant activation lasting to the response time. These results suggest that single item encoding is characterized by transient high frequency ECoG responses, while the maintenance of information during the delay period may be mediated by mechanisms necessitating only low‐levels of neuronal activations. Hum Brain Mapp 36:3988–4003, 2015.

Cortical representation of persistent visual stimuli

Abstract Research into visual neural activity has focused almost exclusively on onset‐ or change‐driven responses and little is known about how information is encoded in the brain during sustained periods of visual perception. We used intracranial recordings in humans to determine the degree to which the presence of a visual stimulus is persistently encoded by neural activity. The correspondence between stimulus duration and neural response duration was strongest in early visual cortex and gradually diminished along the visual hierarchy, such that is was weakest in inferior‐temporal category‐selective regions. A similar posterior‐anterior gradient was found within inferior temporal face‐selective regions, with posterior but not anterior sites showing persistent face‐selective activity. The results suggest that regions that appear uniform in terms of their category selectivity are dissociated by how they temporally represent a stimulus in support of ongoing visual perception, and delineate a large‐scale organizing principle of the ventral visual stream. HighlightsWe investigated sustained cortical responses to variable‐duration visual stimuli.Activity encoding real‐time stimulus presence diminished along the ventral hierarchy.Posterior but not anterior FFA showed face‐selective duration‐tracking activity.The results suggest a posterior‐anterior gradient in cortical temporal dynamics.

Persistent neural activity encoding real-time presence of visual stimuli decays along the ventral stream

Neural populations that encode sensory experience should be persistently active for as long as the experience persists. However, research into visual neural activity has focused almost exclusively on onset-driven responses that cannot account for sustained perception. We used intracranial recordings in humans to determine the degree to which the presence of a visual stimulus is persistently encoded by neural activity. The correspondence between stimulus duration and response duration was strongest in early visual cortex and gradually diminished along the visual hierarchy, such that is was weakest in inferior-temporal category-selective regions. A similar posterior-anterior gradient was found within inferior temporal face-selective regions, with posterior but not anterior sites showing persistent face-selective activity. The results suggest that regions that appear uniform in terms of their category selectivity are dissociated by how they temporally represent a stimulus in support of real-time experience, and delineate a large-scale organizing principle of the ventral visual stream.

Increasing suppression of saccade-related transients along the human visual hierarchy

A key hallmark of visual perceptual awareness is robustness to instabilities arising from unnoticeable eye and eyelid movements. In previous human intracranial (iEEG) work (Golan et al., 2016) we found that excitatory broadband high-frequency activity transients, driven by eye blinks, are suppressed in higher-level but not early visual cortex. Here, we utilized the broad anatomical coverage of iEEG recordings in 12 eye-tracked neurosurgical patients to test whether a similar stabilizing mechanism operates following small saccades. We compared saccades (1.3°−3.7°) initiated during inspection of large individual visual objects with similarly-sized external stimulus displacements. Early visual cortex sites responded with positive transients to both conditions. In contrast, in both dorsal and ventral higher-level sites the response to saccades (but not to external displacements) was suppressed. These findings indicate that early visual cortex is highly unstable compared to higher-level visual regions which apparently constitute the main target of stabilizing extra-retinal oculomotor influences.

Repeated performance in problem-solving tasks attenuates human cortical responses

A ubiquitous characteristic of human cortical networks is their tendency to rapidly change their response properties upon repetition. While this phenomenon has been amply documented using simple sensory-motor tasks, it is still unclear to what extent brain activations change on a short time scale when we are engaged in high level, complex tasks. Here, we examined this question using three types of high-level visual problems. We analyzed data from intracranial recordings performed in eight patients, focusing on the location and type of changes and on their relationship to overt behavior. Our results show significant repetition effects, manifested as signal decrease with repetition, in three different groups of electrodes: Visual sites, which increased their activity during stimuli presentation; Processing Positive sites, which demonstrated increased activity throughout the experimental trial; and Processing Negative sites, which demonstrated suppression of activity during the trial as compared to baseline. Interestingly, despite these significant repetition effects, response time remained unchanged with repetition. These findings bear directly upon our ability to interpret results aggregated across multiple repetitions of the same complex task.