The Relation of Ongoing Brain Activity, Evoked Neural Responses, and Cognition

Ongoing brain activity has been observed since the earliest neurophysiological recordings and is found over a wide range of temporal and spatial scales. It is characterized by remarkably large spontaneous modulations. Here, we review evidence for the functional role of these ongoing activity fluctuations and argue that they constitute an essential property of the neural architecture underlying cognition. The role of spontaneous activity fluctuations is probably best understood when considering both their spatiotemporal structure and their functional impact on cognition. We first briefly argue against a “segregationist” view on ongoing activity, both in time and space, which would selectively associate certain frequency bands or levels of spatial organization with specific functional roles. Instead, we emphasize the functional importance of the full range, from differentiation to integration, of intrinsic activity within a hierarchical spatiotemporal structure. We then highlight the flexibility and context-sensitivity of intrinsic functional connectivity that suggest its involvement in functionally relevant information processing. This role in information processing is pursued by reviewing how ongoing brain activity interacts with afferent and efferent information exchange of the brain with its environment. We focus on the relationship between the variability of ongoing and evoked brain activity, and review recent reports that tie ongoing brain activity fluctuations to variability in human perception and behavior. Finally, these observations are discussed within the framework of the free-energy principle which – applied to human brain function – provides a theoretical account for a non-random, coordinated interaction of ongoing and evoked activity in perception and behavior

Function of BID - a molecule of the bcl-2 family - in ischemic cell death in the brain

Mitochondrial mechanisms, particularly the release of cytochrome c, play a role in the death of nerve and glial cells in cerebral ischemia. We have currently investigated whether BID, a proapoptotic molecule of the bcl-2 family and promoter of the release of cytochrome c is expressed in the brain, activated by cerebral ischemia in vivo, and contributes to ischemic cell death. We found BID in the cytosol of mouse brain and of primary cultured mouse neurons and showed that neuronal BID is a substrate for caspase 8. BID was cleaved in vivo 4 h after transitory occlusion of the middle cerebral artery. Further, BID-/- mice had a significant attenuation of infarction (-67%) and significantly lower release of cytochrome c (-41 %). The findings indicate that the proapoptotic molecule BID may contribute to the demise of nerve cells from cerebral ischemia by release of cytochrome c and activation of caspase. Copyright (C) 2002 S. Karger AG, Basel

Use of HPC to Analyze Changes in Gene Expression during Fruit Fly Spermiogenesis

In the fruit fly, Drosophila melanogaster, JAK/STAT signaling during spermiogenesis is known to play a crucial role in the maintenance of stem cells of the testis. Recent studies in our lab have shown that activation of the JAK/STAT pathway in somatic cyst cells is also required for the later stages of spermiogenesis like individualization. The main goal of this project is to characterize the events downstream of JAK/STAT signaling in spermiogenesis and more specifically to determine the mechanism by which JAK/STAT activation regulates individualization, a later stage in spermiogenesis where 64 individual spermatids are formed from a 64-interconnected spermatid bundle. This study has compared transcriptional profiles of testes in which JAK/STAT signaling has been genetically arrested prior to individualization to testes from wild type flies using RNA-seq methods

Intermittent Motion in Desert Locusts: Behavioural Complexity in Simple Environments

10 páginas, 4 figuras.Animals can exhibit complex movement patterns that may be the result of interactions with their environment or may be directly the mechanism by which their behaviour is governed. In order to understand the drivers of these patterns we examine the movement behaviour of individual desert locusts in a homogenous experimental arena with minimal external cues. Locust motion is intermittent and we reveal that as pauses become longer, the probability that a locust changes direction from its previous direction of travel increases. Long pauses (of greater than 100 s) can be considered reorientation bouts, while shorter pauses (of less than 6 s) appear to act as periods of resting between displacements. We observe powerlaw behaviour in the distribution of move and pause lengths of over 1.5 orders of magnitude. While Le´vy features do exist, locusts’ movement patterns are more fully described by considering moves, pauses and turns in combination. Further analysis reveals that these combinations give rise to two behavioural modes that are organized in time: local search behaviour (long exploratory pauses with short moves) and relocation behaviour (long displacement moves with shorter resting pauses). These findings offer a new perspective on how complex animal movement patterns emerge in nature.The authors acknowledge support from the Natural Environment Research Council (S.B.), the Spanish Ministry of Science and Innovation: MICINN-RyC 2009-04133 and BFU2010-22337 (F.B.) Searle Scholars Award 08-SPP-201 (I.D.C.), National Science Foundation Award PHY-0848755 (I.D.C.), Office of Naval Research Award N00014-09-1-1074 (I.D.C.) and a DARPA Grant No. HR0011-09-1-0055 (to Princeton University) and an Army Research Office Grant W911NG-11-1- 0385 (I.D.C.).Peer reviewe

Functional properties and projections of neurons in the medial amygdala

The medial nucleus of the amygdala (MeA) plays a key role in innate emotional behaviors by relaying olfactory information to hypothalamic nuclei involved in reproduction and defense. However, little is known about the neuronal components of this region or their role in the olfactory-processing circuitry of the amygdala. Here, we have characterized neurons in the posteroventral division of the medial amygdala (MePV) using the GAD67-GFP mouse. Based on their electrophysiological properties and GABA expression, unsupervised cluster analysis divided MePV neurons into three types of GABAergic (Types 1-3) and two non-GABAergic cells (Types I and II). All cell types received olfactory synaptic input from the accessory olfactory bulb and, with the exception of Type 2 GABAergic neurons, sent projections to both reproductive and defensive hypothalamic nuclei. Type 2 GABAergic cells formed a chemically and electrically interconnected network of local circuit inhibitory interneurons that resembled neurogliaform cells of the piriform cortex and provided feedforward inhibition of the olfactory-processing circuitry of the MeA. These findings provide a description of the cellular organization and connectivity of the MePV and further our understanding of amygdala circuits involved in olfactory processing and innate emotions

The Role of Palliative Surgery for Malignant Bowel Obstruction and Perforation in Advanced Microsatellite Instability-High Colorectal Carcinoma in the Era of Immunotherapy: Case Report.

The role of palliative surgery in the management of acute complications in patients with disseminated malignancy remains controversial given the complexity of assessing acute surgical risk and long-term oncologic outcome. With the emergence of checkpoint blockade immunotherapy, there appears to be an increasing role for historically palliative procedures as a bridge to systemic immunotherapy. This is especially evident in advanced microsatellite instability-high (MSI-H) colorectal cancer where malignant obstruction and fistula formation are more common and where immunotherapy with checkpoint blockade (anti-PD-1/PD-L1, anti-CTLA-4) has a high response rate with potential for favorable oncologic outcomes. We present a series of three patients with MSI-H metastatic colorectal cancer complicated by malignant bowel obstruction and fistula formation, who having progressed on standard chemotherapy, underwent palliative intervention as a bridge to immune checkpoint blockade with durable and clinically meaningful anti-cancer responses. These cases highlight the need to re-evaluate the role of historically palliative operations in the setting of disease progression for immunotherapy-responsive tumors

Predictive Coding or Evidence Accumulation? False Inference and Neuronal Fluctuations

Perceptual decisions can be made when sensory input affords an inference about what generated that input. Here, we report findings from two independent perceptual experiments conducted during functional magnetic resonance imaging (fMRI) with a sparse event-related design. The first experiment, in the visual modality, involved forced-choice discrimination of coherence in random dot kinematograms that contained either subliminal or periliminal motion coherence. The second experiment, in the auditory domain, involved free response detection of (non-semantic) near-threshold acoustic stimuli. We analysed fluctuations in ongoing neural activity, as indexed by fMRI, and found that neuronal activity in sensory areas (extrastriate visual and early auditory cortex) biases perceptual decisions towards correct inference and not towards a specific percept. Hits (detection of near-threshold stimuli) were preceded by significantly higher activity than both misses of identical stimuli or false alarms, in which percepts arise in the absence of appropriate sensory input. In accord with predictive coding models and the free-energy principle, this observation suggests that cortical activity in sensory brain areas reflects the precision of prediction errors and not just the sensory evidence or prediction errors per se

Development and properties of functional yoghurt enriched with postbiotic produced by yoghurt cultures using cheese whey and skim milk

This study aimed to examine the effects of supplementation of postbiotics derived from Streptococcus thermophilus (ST) and Lactobacillus delbrueckii subsp. bulgaricus (LB) in cheese whey (CW) and skim milk (SM) on antioxidant activity, viability of yoghurt starters, and quality parameters of low-fat yoghurt during 22 days of storage. The LB-CW (L delbrueckii ssp. bulgaricus postbiotic-containing cheese whey) sample exhibited the highest antioxidant activity, with 18.71% inhibition (p > 0.05). This sample also showed the highest water holding capacity (77.93%; p < 0.05) and a trend toward receiving the most favorable sensory attributes (p > 0.05) compared to the other samples. The LB-CW and LB-SM yoghurt samples exhibited significantly higher body and texture scores compared to the ST-SM-fortified yoghurt (p < 0.05). However, there was no significant difference in the overall acceptability of the LB-SM and ST-SM yoghurt samples across both starters (p > 0.05). Such findings highlight the potential of postbiotics as functional ingredients to enhance the nutritional and sensory aspects of yoghurt, further contributing to its appeal as a health-promoting product