Biology subjects

Cohen, M. A.

Publications and source records attributed to Cohen, M. A..

6 recordsLinked to original sources

bioRxiv2023

A novel signature of visual awareness independent of post-perceptual processing

What are the neural processes associated with perceptual awareness that are distinct from pre-conscious sensory encoding and post-perceptual processes such as reporting an experience? Here, we used electroencephalography (EEG) and a no-report visual masking paradigm with parametric manipulations of stimulus visibility to search for neural signatures associated with perceptual awareness independent from both early sensory processing and subsequent reporting. Specifically, we manipulated the time between stimuli and subsequent masks in a linear manner (i.e., 17ms, 33ms, 50ms, 67ms, and 83ms) such that observers awareness of the stimuli increased in a non-linear fashion (i.e., stimuli were never seen at the two shortest time intervals, always seen at the two longest intervals, and seen approximately 50% of the time at the intermediate interval). Moreover, we manipulated the task across blocks to create separate report and no-report conditions. Overall, we found one neural signal that was closely associated with perceptual awareness, independent from the task: a fronto-central event-related potential (ERP), from [~]250-300ms, that we refer to as the N2. In contrast, earlier ERP signals were linked with the linear manipulation of stimulus strength regardless of visibility, while later candidate signatures, such as P3b and temporal generalization of decoding, were present in the report condition but absent in the no-report condition suggesting a closer association with task performance than perceptual awareness. Taken together, these findings inform current debates regarding theories of consciousness and offer new avenues for exploring the neural mechanisms supporting conscious processing. Significance statementWhat differentiates conscious and unconscious processing in the brain? Here, we identify an electrophysiological signature of perceptual awareness using a combination of visual psychophysics and electroencephalography (EEG). In addition, we used a newly developed "no-report" paradigm, in which observers did not report anything about their perceptual experience to separate neural signals associated with consciousness from those associated with the act of reporting (i.e., memory, motor planning, etc.). Using this no-report paradigm was critical because several other candidate signatures of conscious processing were present when observers reported their experiences but completely disappeared when observers did not report their experiences. These findings open the door to future research interested in the neural mechanisms associated of conscious processing.

neuroscience↗

bioRxiv2021

Face-Selective Responses Present in Multiple Regions of the Human Infant Brain

In human adults, multiple cortical regions respond robustly to faces, including the occipital face area (OFA) and fusiform face area (FFA), implicated in face perception, and the superior temporal sulcus (STS) and medial prefrontal cortex (MPFC), implicated in higher level social functions. When in development does face selectivity arise in each of these regions? Here, we combined two awake infant functional magnetic resonance neuroimaging (fMRI) datasets to create a sample size twice the size of previous reports (n=65 infants, 2.6-9.6 months). Infants watched movies of faces, bodies, objects, and scenes while fMRI data were collected. Despite variable amounts of data from each infant, individual subject whole-brain activations maps revealed a significant response to faces compared to non-face visual categories in the approximate location of OFA, FFA, STS, and MPFC. To determine the strength and nature of face selectivity in these regions, we used cross-validated functional region of interest (fROI) analyses. Across this larger sample size, face responses in OFA, FFA, STS, and MPFC were significantly greater than responses to bodies, objects, and scenes. Even the youngest infants (2-5 months) showed significantly face-selective responses in FFA, STS, and MPFC, but not OFA. These results demonstrate that face selectivity is present in multiple cortical regions within months of birth, providing powerful constraints on theories of cortical development. Significance StatementSocial cognition often begins with face perception. In adults, several cortical regions respond robustly to faces, yet little is known about when and how these regions first arise in development. To test whether face selectivity changes in the first year of life, we combined two datasets, doubling the sample size relative to previous reports. In the approximate location of the fusiform face area (FFA), superior temporal sulcus (STS), and medial prefrontal cortex (MPFC) but not occipital face area (OFA), face selectivity was present in the youngest group. These findings demonstrate that face-selective responses are present across multiple lobes of the brain very early in life.

neuroscience↗

bioRxiv2021

Invariant Representation of Physical Stability in the Human Brain

Successful engagement with the world requires the ability to predict what will happen next. Here we investigate how the brain makes the most basic prediction about the physical world: whether the situation in front of us is stable, and hence likely to stay the same, or unstable, and hence likely to change in the immediate future. Specifically, we ask if judgements of stability can be supported by the kinds of representations that have proven to be highly effective at visual object recognition in both machines and brains, or instead if the ability to determine the physical stability of natural scenes may require generative algorithms that simulate the physics of the world. To find out, we measured responses in both convolutional neural networks (CNNs) and the brain (using fMRI) to natural images of physically stable versus unstable scenarios. We find no evidence for generalizable representations of physical stability in either standard CNNs trained on visual object and scene classification (ImageNet), or in the human ventral visual pathway, which has long been implicated in the same process. However, in fronto-parietal regions previously implicated in intuitive physical reasoning we find both scenario-invariant representations of physical stability, and higher univariate responses to unstable than stable scenes. These results demonstrate abstract representations of physical stability in the dorsal but not ventral pathway, consistent with the hypothesis that the computations underlying stability entail not just pattern classification but forward physical simulation.

neuroscience↗

bioRxiv2021

Cell lineage as a predictor of immune response in neuroblastoma

Immunotherapy for patients with neuroblastoma has met with limited success, partly due to an incomplete understanding of the mechanisms underlying immune responsiveness in this clinically and genetically heterogenic tumor. Here, we undertook an unbiased analysis using dimension reduction and UMAP visualization of transcriptional signatures derived from 498 primary neuroblastoma tumors. Four distinct clusters based on differentially expressed genes emerged, of which one, representing about 30% and comprising mainly of MYCN-nonamplified tumors, was notable for the high expression of genes associated with both immune response activation and suppression. This capacity to elicit a productive immune response resided exclusively in tumors with dominant populations of undifferentiated, neural crest-like or mesenchymal cells; by contrast, tumors comprising primarily of committed, adrenergic neuron-like cells were less immunogenic. Mesenchymal neuroblastoma cells were enriched for innate and adaptive immune gene signatures, demonstrated engagement with cytotoxic T and natural killer cells, and induced immune cell infiltration in an immunocompetent mouse model. Transcriptional or targeted therapy-induced reprogramming of adrenergic cells to the mesenchymal state led to reactivation of tumor cell-intrinsic immune genes. Key immune response genes in adrenergic tumor cells were found to be epigenetically silenced by the PRC2 complex, and such repression could be relieved by either mesenchymal cell state reprogramming or EZH2 inhibition, leading to increased activation of natural killer cells by the tumor cells. These data identify cell lineage as a major determinant of the immunogenic potential in neuroblastoma that could be used to stratify patients who are most likely to benefit from immunotherapy.

cancer biology↗

bioRxiv2020

Distinguishing the neural correlates of perceptual awareness and post-perceptual processing

To identify the neural correlates of perceptual awareness, researchers often compare the differences in neural activation between conditions in which an observer is or is not aware of a stimulus. While intuitive, this approach often contains a critical limitation: In order to link brain activity with perceptual awareness, observers traditionally report the contents of their perceptual experience. However, relying on observers reports is problematic because it is difficult to know if the neural responses being measured are associated with conscious perception or with post-perceptual processes involved in the reporting task (i.e., working memory, decision-making, etc.). To address this issue, we combined a standard visual masking paradigm with a recently developed "no-report" paradigm in male/female human participants. In the visual masking paradigm, observers saw images of animals and objects that were visible or invisible depending on their proximity to masks. Meanwhile, on half of the trials, observers reported the contents of their perceptual experience (i.e., report condition), while on the other half of trials they refrained from reporting about their experiences (i.e., no-report condition). We used electroencephalography (EEG) to examine how visibility interacts with reporting by measuring the P3b event related potential (ERP), one of the proposed canonical "signatures" of conscious processing. Overall, we found a robust P3b in the report condition, but no P3b whatsoever in the no-report condition. This finding suggests that the P3b itself is not a neural signature of conscious processing and highlights the importance of carefully distinguishing the neural correlates of perceptual awareness from post-perceptual processing. Significance statementWhat are the neural signatures that differentiate conscious and unconscious processing in the brain? Perhaps the most well-established candidate signature is the P3b event-related potential (ERP), a late slow wave that appears when observers are aware of a stimulus, but disappears when a stimulus fails to reach awareness. Here, however, we found that the P3b does not track what observers are perceiving but instead tracks what observers are reporting. When observers are aware of simple visual stimuli, the P3b is nowhere to be found unless observers are reporting the contents of their experience. These results challenge the well-established notion of the P3b as a neural marker of awareness and highlight the need for new approaches to the neuroscience of consciousness.

neuroscience↗

bioRxiv2019

Development of Human Neuroblastomas in Mouse-Human Neural Crest Chimeras

Neuroblastoma (NB), derived from the neural crest (NC), is the most common pediatric extracranial solid tumor. Here we establish a platform that allows studying human NBs in mouse-human NC chimeras. Chimeric mice were produced by injecting human NC cells carrying NB relevant oncogenes in-utero into gastrulating mouse embryos. The mice developed tumors composed of a heterogenous cell population that closely resembled that seen in primary NBs of patients but were significantly different from homogenous tumors formed in xenotransplantation models. The human tumors emerged in immunocompetent hosts and were extensively infiltrated by mouse cytotoxic T cells reflecting a vigorous host anti-tumor immune response. However, the tumors blunted the immune response by inducing infiltration of regulatory T cells and expression of immune checkpoints similar to escape mechanisms seen in human cancer patients. Thus, this experimental platform allows studying human tumor initiation, progression, manifestation and tumor - immune-system interactions in an animal model system.

cancer biology↗