An ecological investigation of the capacity to follow simultaneous speech and preferential detection of ones' own name.

Many situations require focusing attention on one speaker, while monitoring the environment for potentially important information. Some have proposed that dividing attention among 2 speakers involves behavioral trade-offs, due to limited cognitive resources. However the severity of these trade-offs, particularly under ecologically-valid circumstances, is not well understood. We investigated the capacity to process simultaneous speech using a dual-task paradigm simulating task-demands and stimuli encountered in real-life. Participants listened to conversational narratives (Narrative Stream) and monitored a stream of announcements (Barista Stream), to detect when their order was called. We measured participants' performance, neural activity, and skin conductance as they engaged in this dual-task. Participants achieved extremely high dual-task accuracy, with no apparent behavioral trade-offs. Moreover, robust neural and physiological responses were observed for target-stimuli in the Barista Stream, alongside significant neural speech-tracking of the Narrative Stream. These results suggest that humans have substantial capacity to process simultaneous speech and do not suffer from insufficient processing resources, at least for this highly ecological task-combination and level of perceptual load. Results also confirmed the ecological validity of the advantage for detecting ones' own name at the behavioral, neural, and physiological level, highlighting the contribution of personal relevance when processing simultaneous speech.

Listening to two speakers: Capacity and tradeoffs in neural speech tracking during Selective and Distributed Attention.

Speech comprehension is severely compromised when several people talk at once, due to limited perceptual and cognitive resources. In such circumstances, top-down attention mechanisms can actively prioritize processing of task-relevant speech. However, behavioral and neural evidence suggest that this selection is not exclusive, and the system may have sufficient capacity to process additional speech input as well. Here we used a data-driven approach to contrast two opposing hypotheses regarding the system's capacity to co-represent competing speech: Can the brain represent two speakers equally or is the system fundamentally limited, resulting in tradeoffs between them? Neural activity was measured using magnetoencephalography (MEG) as human participants heard concurrent speech narratives and engaged in two tasks: Selective Attention, where only one speaker was task-relevant and Distributed Attention, where both speakers were equally relevant. Analysis of neural speech-tracking revealed that both tasks engaged a similar network of brain regions involved in auditory processing, attentional control and speech processing. Interestingly, during both Selective and Distributed Attention the neural representation of competing speech showed a bias towards one speaker. This is in line with proposed 'bottlenecks' for co-representation of concurrent speech and suggests that good performance on distributed attention tasks may be achieved by toggling attention between speakers over time.

Synaptic size dynamics as an effectively stochastic process.

Long-term, repeated measurements of individual synaptic properties have revealed that synapses can undergo significant directed and spontaneous changes over time scales of minutes to weeks. These changes are presumably driven by a large number of activity-dependent and independent molecular processes, yet how these processes integrate to determine the totality of synaptic size remains unknown. Here we propose, as an alternative to detailed, mechanistic descriptions, a statistical approach to synaptic size dynamics. The basic premise of this approach is that the integrated outcome of the myriad of processes that drive synaptic size dynamics are effectively described as a combination of multiplicative and additive processes, both of which are stochastic and taken from distributions parametrically affected by physiological signals. We show that this seemingly simple model, known in probability theory as the Kesten process, can generate rich dynamics which are qualitatively similar to the dynamics of individual glutamatergic synapses recorded in long-term time-lapse experiments in ex-vivo cortical networks. Moreover, we show that this stochastic model, which is insensitive to many of its underlying details, quantitatively captures the distributions of synaptic sizes measured in these experiments, the long-term stability of such distributions and their scaling in response to pharmacological manipulations. Finally, we show that the average kinetics of new postsynaptic density formation measured in such experiments is also faithfully captured by the same model. The model thus provides a useful framework for characterizing synapse size dynamics at steady state, during initial formation of such steady states, and during their convergence to new steady states following perturbations. These findings show the strength of a simple low dimensional statistical model to quantitatively describe synapse size dynamics as the integrated result of many underlying complex processes.

Adaptation to prolonged neuromodulation in cortical cultures: an invariable return to network synchrony.

BACKGROUND: Prolonged neuromodulatory regimes, such as those critically involved in promoting arousal and suppressing sleep-associated synchronous activity patterns, might be expected to trigger adaptation processes and, consequently, a decline in neuromodulator-driven effects. This possibility, however, has rarely been addressed. RESULTS: Using networks of cultured cortical neurons, acetylcholine microinjections and a novel closed-loop 'synchrony-clamp' system, we found that acetylcholine pulses strongly suppressed network synchrony. Over the course of many hours, however, synchrony invariably reemerged, even when feedback was used to compensate for declining cholinergic efficacy. Network synchrony also reemerged following its initial suppression by noradrenaline, but this did not occlude the suppression of synchrony or its gradual reemergence following subsequent cholinergic input. Importantly, cholinergic efficacy could be restored and preserved over extended time scales by periodically withdrawing cholinergic input. CONCLUSIONS: These findings indicate that the capacity of neuromodulators to suppress network synchrony is constrained by slow-acting, reactive processes. A multiplicity of neuromodulators and ultimately neuromodulator withdrawal periods might thus be necessary to cope with an inevitable reemergence of network synchrony.

Long-term relationships between synaptic tenacity, synaptic remodeling, and network activity.

Synaptic plasticity is widely believed to constitute a key mechanism for modifying functional properties of neuronal networks. This belief implicitly implies, however, that synapses, when not driven to change their characteristics by physiologically relevant stimuli, will maintain these characteristics over time. How tenacious are synapses over behaviorally relevant time scales? To begin to address this question, we developed a system for continuously imaging the structural dynamics of individual synapses over many days, while recording network activity in the same preparations. We found that in spontaneously active networks, distributions of synaptic sizes were generally stable over days. Following individual synapses revealed, however, that the apparently static distributions were actually steady states of synapses exhibiting continual and extensive remodeling. In active networks, large synapses tended to grow smaller, whereas small synapses tended to grow larger, mainly during periods of particularly synchronous activity. Suppression of network activity only mildly affected the magnitude of synaptic remodeling, but dependence on synaptic size was lost, leading to the broadening of synaptic size distributions and increases in mean synaptic size. From the perspective of individual neurons, activity drove changes in the relative sizes of their excitatory inputs, but such changes continued, albeit at lower rates, even when network activity was blocked. Our findings show that activity strongly drives synaptic remodeling, but they also show that significant remodeling occurs spontaneously. Whereas such spontaneous remodeling provides an explanation for "synaptic homeostasis" like processes, it also raises significant questions concerning the reliability of individual synapses as sites for persistently modifying network function.

Author Correction: Dynamics of social representation in the mouse prefrontal cortex.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Dynamics of social representation in the mouse prefrontal cortex.

The prefrontal cortex (PFC) plays an important role in regulating social functions in mammals, and its dysfunction has been linked to social deficits in neurodevelopmental disorders. Yet little is known of how the PFC encodes social information and how social representations may be altered in such disorders. Here, we show that neurons in the medial PFC of freely behaving male mice preferentially respond to socially relevant olfactory cues. Population activity patterns in this region differed between social and nonsocial stimuli and underwent experience-dependent refinement. In mice lacking the autism-associated gene Cntnap2, both the categorization of sensory stimuli and the refinement of social representations were impaired. Noise levels in spontaneous population activity were higher in Cntnap2 knockouts and correlated with the degree to which social representations were disrupted. Our findings elucidate the encoding of social sensory cues in the medial PFC and provide a link between altered prefrontal dynamics and autism-associated social dysfunction.

Pomegranate oil analysis with emphasis on MALDI-TOF/MS triacylglycerol fingerprinting.

Pomegranate oil (PGO) is a unique and quite rare edible oil produced from Punica granatum L. seeds. It is considered to be a powerful health-benefiting agent, due to its antioxidative, anticancer, and antilipidemic properties. The aim of this study was to achieve a comprehensive and detailed profile of the different components of PGO. The fatty acid profile and phytosterol composition were determined by GC-MS; the triacylglycerol (TAG) compositions were profiled by the mass spectrometry tool of MALDI-TOF/MS. Results showed linolenic acid (18:3) to be the predominant fatty acid in the PGO (64-83%), as previously reported. The linolenic acid fraction was composed of four different chromatographically separated peaks that are assumed, according to MS data (based on both FAME and DMOX derivatization), to be attributed to different geometric isomers of conjugated linolenic acid (CLNA), punicic acid (18:3: 9-cis,11-trans,13-cis) being the major isomer. The MALDI-TOF/MS finger printing results showed the different TAG compositions present in the PGO, the major ones being LnLnLn and LnLnP. This unique PGO TAG fingerprint enables it to be differentiated from most other common edible oils. Phytosterols were found in quite a high concentration in the PGO (4089-6205 mg/kg), about 3-4-fold higher than in soybean oil. A detailed profile of the phytosterols in the PGO showed a wide variety, the major phytosterols being beta-sitosterol, campesterol, and stigmasterol. This study depicts a new detailed analysis of PGO, showing great potential for further research regarding the physiological effects of specific valuable components in pomegranate oil.

Long-term relationships between cholinergic tone, synchronous bursting and synaptic remodeling.

Cholinergic neuromodulation plays key roles in the regulation of neuronal excitability, network activity, arousal, and behavior. On longer time scales, cholinergic systems play essential roles in cortical development, maturation, and plasticity. Presumably, these processes are associated with substantial synaptic remodeling, yet to date, long-term relationships between cholinergic tone and synaptic remodeling remain largely unknown. Here we used automated microscopy combined with multielectrode array recordings to study long-term relationships between cholinergic tone, excitatory synapse remodeling, and network activity characteristics in networks of cortical neurons grown on multielectrode array substrates. Experimental elevations of cholinergic tone led to the abrupt suppression of episodic synchronous bursting activity (but not of general activity), followed by a gradual growth of excitatory synapses over hours. Subsequent blockage of cholinergic receptors led to an immediate restoration of synchronous bursting and the gradual reversal of synaptic growth. Neither synaptic growth nor downsizing was governed by multiplicative scaling rules. Instead, these occurred in a subset of synapses, irrespective of initial synaptic size. Synaptic growth seemed to depend on intrinsic network activity, but not on the degree to which bursting was suppressed. Intriguingly, sustained elevations of cholinergic tone were associated with a gradual recovery of synchronous bursting but not with a reversal of synaptic growth. These findings show that cholinergic tone can strongly affect synaptic remodeling and synchronous bursting activity, but do not support a strict coupling between the two. Finally, the reemergence of synchronous bursting in the presence of elevated cholinergic tone indicates that the capacity of cholinergic neuromodulation to indefinitely suppress synchronous bursting might be inherently limited.