Cortical mechanisms of sensory learning and object recognition

Learning about the world through our senses constrains our ability to recognise our surroundings. Experience shapes perception. What is the neural basis for object recognition and how are learning-induced changes in recognition manifested in neural populations? We consider first the location of neurons that appear to be critical for object recognition, before describing what is known about their function. Two complementary processes of object recognition are considered: discrimination among diagnostic object features and generalization across non-diagnostic features. Neural plasticity appears to underlie the development of discrimination and generalization for a given set of features, though tracking these changes directly over the course of learning has remained an elusive task

Category-Specific Responses to Faces and Objects in Primate Auditory Cortex

Auditory and visual signals often occur together, and the two sensory channels are known to influence each other to facilitate perception. The neural basis of this integration is not well understood, although other forms of multisensory influences have been shown to occur at surprisingly early stages of processing in cortex. Primary visual cortex neurons can show frequency-tuning to auditory stimuli, and auditory cortex responds selectively to certain somatosensory stimuli, supporting the possibility that complex visual signals may modulate early stages of auditory processing. To elucidate which auditory regions, if any, are responsive to complex visual stimuli, we recorded from auditory cortex and the superior temporal sulcus while presenting visual stimuli consisting of various objects, neutral faces, and facial expressions generated during vocalization. Both objects and conspecific faces elicited robust field potential responses in auditory cortex sites, but the responses varied by category: both neutral and vocalizing faces had a highly consistent negative component (N100) followed by a broader positive component (P180) whereas object responses were more variable in time and shape, but could be discriminated consistently from the responses to faces. The face response did not vary within the face category, i.e., for expressive vs. neutral face stimuli. The presence of responses for both objects and neutral faces suggests that auditory cortex receives highly informative visual input that is not restricted to those stimuli associated with auditory components. These results reveal selectivity for complex visual stimuli in a brain region conventionally described as non-visual “unisensory” cortex

xDGP: A Dynamic Graph Processing System with Adaptive Partitioning

13 pagesMany real-world systems, such as social networks, rely on mining efficiently large graphs, with hundreds of millions of vertices and edges. This volume of information requires partitioning the graph across multiple nodes in a distributed system. This has a deep effect on performance, as traversing edges cut between partitions incurs a significant performance penalty due to the cost of communication. Thus, several systems in the literature have attempted to improve computational performance by enhancing graph partitioning, but they do not support another characteristic of real-world graphs: graphs are inherently dynamic, their topology evolves continuously, and subsequently the optimum partitioning also changes over time. In this work, we present the first system that dynamically repartitions massive graphs to adapt to structural changes. The system optimises graph partitioning to prevent performance degradation without using data replication. The system adopts an iterative vertex migration algorithm that relies on local information only, making complex coordination unnecessary. We show how the improvement in graph partitioning reduces execution time by over 50%, while adapting the partitioning to a large number of changes to the graph in three real-world scenarios

Individuation and holistic processing of faces in rhesus monkeys

Despite considerable evidence that neural activity in monkeys reflects various aspects of face perception, relatively little is known about monkeys' face processing abilities. Two characteristics of face processing observed in humans are a subordinate-level entry point, here, the default recognition of faces at the subordinate, rather than basic, level of categorization, and holistic effects, i.e. perception of facial displays as an integrated whole. The present study used an adaptation paradigm to test whether untrained rhesus macaques (Macaca mulatta) display these hallmarks of face processing. In experiments 1 and 2, macaques showed greater rebound from adaptation to conspecific faces than to other animals at the individual or subordinate level. In experiment 3, exchanging only the bottom half of a monkey face produced greater rebound in aligned than in misaligned composites, indicating that for normal, aligned faces, the new bottom half may have influenced the perception of the whole face. Scan path analysis supported this assertion: during rebound, fixation to the unchanged eye region was renewed, but only for aligned stimuli. These experiments show that macaques naturally display the distinguishing characteristics of face processing seen in humans and provide the first clear demonstration that holistic information guides scan paths for conspecific faces

Whole-Brain Multimodal Neuroimaging Model Using Serotonin Receptor Maps Explains Non-linear Functional Effects of LSD

Understanding the underlying mechanisms of the human brain in health and disease will require models with necessary and sufficient details to explain how function emerges from the underlying anatomy and is shaped by neuromodulation. Here, we provide such a detailed causal explanation using a whole-brain model integrating multimodal imaging in healthy human participants undergoing manipulation of the serotonin system. Specifically, we combined anatomical data from diffusion magnetic resonance imaging (dMRI) and functional magnetic resonance imaging (fMRI) with neurotransmitter data obtained with positron emission tomography (PET) of the detailed serotonin 2A receptor (5-HT2AR) density map. This allowed us to model the resting state (with and without concurrent music listening) and mechanistically explain the functional effects of 5-HT2AR stimulation with lysergic acid diethylamide (LSD) on healthy participants. The whole-brain model used a dynamical mean-field quantitative description of populations of excitatory and inhibitory neurons as well as the associated synaptic dynamics, where the neuronal gain function of the model is modulated by the 5-HT2AR density. The model identified the causative mechanisms for the non-linear interactions between the neuronal and neurotransmitter system, which are uniquely linked to (1) the underlying anatomical connectivity, (2) the modulation by the specific brainwide distribution of neurotransmitter receptor density, and (3) the non-linear interactions between the two. Taking neuromodulatory activity into account when modeling global brain dynamics will lead to novel insights into human brain function in health and disease and opens exciting possibilities for drug discovery and design in neuropsychiatric disorders.ERC Advanced Grant DYSTRUCTURE (295129), the Spanish Research ProjectPSI2016-75688-P, and the European Union’s Horizon 2020 Framework Programme for Research and Innovation under the Specific Grant Agreement No. 785907 (Human Brain Project SGA2). ERC Consolidator Grant: CAREGIVING (615539) and Center for Music in the Brain, funded by the Danish National Research Foundation (DNRF117). Alex Mosley Charitable Trust, and the study that yielded the empirical LSD data was carried out as part of a Beckley-Imperial research collaboration. J. Cabral is supported under the project NORTE-01-0145-FEDER-000023 from the Northern Portugal Regional Operational Program (NORTE 2020) under the Portugal 2020 Partnership Agreement through the European Regional Development Fund (FEDER). Cimbi database were supported by a centre grant from the Lundbeck Foundation (2010-5364

Ready ... Go: Amplitude of the fMRI Signal Encodes Expectation of Cue Arrival Time

What happens when the brain awaits a signal of uncertain arrival time, as when a sprinter waits for the starting pistol? And what happens just after the starting pistol fires? Using functional magnetic resonance imaging (fMRI), we have discovered a novel correlate of temporal expectations in several brain regions, most prominently in the supplementary motor area (SMA). Contrary to expectations, we found little fMRI activity during the waiting period; however, a large signal appears after the “go” signal, the amplitude of which reflects learned expectations about the distribution of possible waiting times. Specifically, the amplitude of the fMRI signal appears to encode a cumulative conditional probability, also known as the cumulative hazard function. The fMRI signal loses its dependence on waiting time in a “countdown” condition in which the arrival time of the go cue is known in advance, suggesting that the signal encodes temporal probabilities rather than simply elapsed time. The dependence of the signal on temporal expectation is present in “no-go” conditions, demonstrating that the effect is not a consequence of motor output. Finally, the encoding is not dependent on modality, operating in the same manner with auditory or visual signals. This finding extends our understanding of the relationship between temporal expectancy and measurable neural signals

Tissue Effects in a Randomized Controlled Trial of Short-term Finasteride in Early Prostate Cancer.

BackgroundIn the Prostate Cancer Prevention Trial, finasteride selectively suppressed low-grade prostate cancer and significantly reduced the incidence of prostate cancer in men treated with finasteride compared with placebo. However, an apparent increase in high-grade disease was also observed among men randomized to finasteride. We aimed to determine why and hypothesized that there is a grade-dependent response to finasteride.MethodsFrom 2007 to 2012, we randomized dynamically by intranet-accessible software 183 men with localized prostate cancer to receive 5mg finasteride or placebo daily in a double-blind study during the 4-6weeks preceding prostatectomy. As the primary end point, the expression of a predefined molecular signature (ERβ, UBE2C, SRD5A2, and VEGF) differentiating high- and low-grade tumors in Gleason grade (GG) 3 areas of finasteride-exposed tumors from those in GG3 areas of placebo-exposed tumors, adjusted for Gleason score (GS) at prostatectomy, was compared. We also determined androgen receptor (AR) levels, Ki-67, and cleaved caspase 3 to evaluate the effects of finasteride on the expression of its downstream target, cell proliferation, and apoptosis, respectively. The expression of these markers was also compared across grades between and within treatment groups. Logistic regression was used to assess the expression of markers.FindingsWe found that the predetermined molecular signature did not distinguish GG3 from GG4 areas in the placebo group. However, AR expression was significantly lower in the GG4 areas of the finasteride group than in those of the placebo group. Within the finasteride group, AR expression was also lower in GG4 than in GG3 areas, but not significantly. Expression of cleaved caspase 3 was significantly increased in both GG3 and GG4 areas in the finasteride group compared to the placebo group, although it was lower in GG4 than in GG3 areas in both groups.InterpretationWe showed that finasteride's effect on apoptosis and AR expression is tumor grade dependent after short-term intervention. This may explain finasteride's selective suppression of low-grade tumors observed in the PCPT

Pain outcomes in patients with bone metastases from advanced cancer: assessment and management with bone-targeting agents

Bone metastases in advanced cancer frequently cause painful complications that impair patient physical activity and negatively affect quality of life. Pain is often underreported and poorly managed in these patients. The most commonly used pain assessment instruments are visual analogue scales, a single-item measure, and the Brief Pain Inventory Questionnaire-Short Form. The World Health Organization analgesic ladder and the Analgesic Quantification Algorithm are used to evaluate analgesic use. Bone-targeting agents, such as denosumab or bisphosphonates, prevent skeletal complications (i.e., radiation to bone, pathologic fractures, surgery to bone, and spinal cord compression) and can also improve pain outcomes in patients with metastatic bone disease. We have reviewed pain outcomes and analgesic use and reported pain data from an integrated analysis of randomized controlled studies of denosumab versus the bisphosphonate zoledronic acid (ZA) in patients with bone metastases from advanced solid tumors. Intravenous bisphosphonates improved pain outcomes in patients with bone metastases from solid tumors. Compared with ZA, denosumab further prevented pain worsening and delayed the need for treatment with strong opioids. In patients with no or mild pain at baseline, denosumab reduced the risk of increasing pain severity and delayed pain worsening along with the time to increased pain interference compared with ZA, suggesting that use of denosumab (with appropriate calcium and vitamin D supplementation) before patients develop bone pain may improve outcomes. These data also support the use of validated pain assessments to optimize treatment and reduce the burden of pain associated with metastatic bone disease