Learning and generation of temporal sequences in the neocortex

The temporal structure of neuronal activity plays a fundamental role in brain function. In addition to the compelling structure found in birdsong, repeating temporal sequences have been experimentally observed in the mammalian neocortex, both at the levels of local field potentials and individual neurons.\ud \ud The mechanisms underlying the learning and generation of temporal sequences are currently unknown. An attractive idea is that time-asymmetric Hebbian mechanisms capture the temporal structure of afferent signals by selectively strengthening the connections between sequentially activated neuronal populations. We explore some consequences of this idea using a simplified model of neocortex.\ud \ud Our model uses excitatory and inhibitory firing rate variables, along with adaptation and time-asymmetric Hebbian plasticity to create a versatile pattern generator which can store and reconstruct input sequences. We study several related properties of this model, mainly: 1) the formation of intersecting and complex sequences, 2) how the structure in the connection matrix affects the dynamics of the system and the symmetries observed in the activity of the network, 3) pathological behaviors due to abnormalities in plasticity and inhibition; the possible relation with epilepsy

THE SHMUSHKEVICH METHOD FOR HIGHER SYMMETRY GROUPS OF INTERACTING PARTICLES

About 60 years ago, I. Shmushkevich presented a simple ingenious method for computing the relative probabilities of channels involving the same interacting multiplets of particles, without the need to compute the Clebsch-Gordan coefficients. The basic idea of Shmushkevich is “isotopic non-polarization” of the states before the interaction and after it. Hence his underlying Lie group was SU(2). We extend this idea to any simple Lie group. This paper determines the relative probabilities of various channels of scattering and decay processes following from the invariance of the interactions with respect to a compact simple a Lie group. Aiming at the probabilities rather than at the Clebsch-Gordan coefficients makes the task easier, and simultaneous consideration of all possible channels for given multiplets involved in the process, makes the task possible. The probability of states with multiplicities greater than 1 is averaged over. Examples with symmetry groups O(5), F(4), and E(8) are shown

Reducing False Recognition in the Deese-Roediger/McDermott Paradigm: Related Lures Reveal How Distinctive Encoding Improves Encoding and Monitoring Processes

In the Deese-Roediger/McDermott (DRM) paradigm, distinctive encoding of list items typically reduces false recognition of critical lures relative to a read-only control. This reduction can be due to enhanced item-specific processing, reduced relational processing, and/or increased test-based monitoring. However, it is unclear whether distinctive encoding reduces false recognition in a selective or global manner. To examine this question, participants studied DRM lists using a distinctive item-specific anagram generation task and then completed a recognition test which included both DRM critical lures and either strongly related lures (Experiment 1) or weakly related lures (Experiment 2). Compared to a read-control group, the generate groups showed increased correct recognition and decreased false recognition of all lure types. We then estimated the separate contributions of encoding and retrieval processes using signal-detection indices. Generation improved correct recognition by both increasing encoding of memory information for list words and by increasing memory monitoring at test. Generation reduced false recognition by reducing the encoding of memory information and by increasing memory monitoring at test. The reduction in false recognition was equivalent for critical lures and related lures, indicating that generation globally reduces the encoding of related non-presented items at study (not just critical lures), while globally increasing list-theme-based monitoring at test

Getting at the Source of Distinctive Encoding Effects in the DRM Paradigm: Evidence From Signal-Detection Measures and Source Judgments

Studying Deese–Roediger–McDermott (DRM) lists using a distinctive encoding task can reduce the DRM false memory illusion. Reductions for both distinctively encoded lists and non-distinctively encoded lists in a within-group design have been ascribed to use of a distinctiveness heuristic by which participants monitor their memories at test for distinctive-task details. Alternatively, participants might simply set a more conservative response criterion, which would be exceeded by distinctive list items more often than all other test items, including the critical non-studied items. To evaluate these alternatives, we compared a within-group who studied 5 lists by reading, 5 by anagram generation, and 5 by imagery, relative to a control group who studied all 15 lists by reading. Generation and imagery improved recognition accuracy by impairing relational encoding, but the within group did not show greater memory monitoring at test relative to the read control group. Critically, the within group’s pattern of list-based source judgments provided new evidence that participants successfully monitored for distinctive-task details at test. Thus, source judgments revealed evidence of qualitative, recollection-based monitoring in the within group, to which our quantitative signal-detection measure of monitoring was blind

Prefrontal Cortex and Somatosensory Cortex in Tactile Crossmodal Association: An Independent Component Analysis of ERP Recordings

Our previous studies on scalp-recorded event-related potentials (ERPs) showed that somatosensory N140 evoked by a tactile vibration in working memory tasks was enhanced when human subjects expected a coming visual stimulus that had been paired with the tactile stimulus. The results suggested that such enhancement represented the cortical activities involved in tactile-visual crossmodal association. In the present study, we further hypothesized that the enhancement represented the neural activities in somatosensory and frontal cortices in the crossmodal association. By applying independent component analysis (ICA) to the ERP data, we found independent components (ICs) located in the medial prefrontal cortex (around the anterior cingulate cortex, ACC) and the primary somatosensory cortex (SI). The activity represented by the IC in SI cortex showed enhancement in expectation of the visual stimulus. Such differential activity thus suggested the participation of SI cortex in the task-related crossmodal association. Further, the coherence analysis and the Granger causality spectral analysis of the ICs showed that SI cortex appeared to cooperate with ACC in attention and perception of the tactile stimulus in crossmodal association. The results of our study support with new evidence an important idea in cortical neurophysiology: higher cognitive operations develop from the modality-specific sensory cortices (in the present study, SI cortex) that are involved in sensation and perception of various stimuli

Working Memory Cells' Behavior May Be Explained by Cross-Regional Networks with Synaptic Facilitation

Neurons in the cortex exhibit a number of patterns that correlate with working memory. Specifically, averaged across trials of working memory tasks, neurons exhibit different firing rate patterns during the delay of those tasks. These patterns include: 1) persistent fixed-frequency elevated rates above baseline, 2) elevated rates that decay throughout the tasks memory period, 3) rates that accelerate throughout the delay, and 4) patterns of inhibited firing (below baseline) analogous to each of the preceding excitatory patterns. Persistent elevated rate patterns are believed to be the neural correlate of working memory retention and preparation for execution of behavioral/motor responses as required in working memory tasks. Models have proposed that such activity corresponds to stable attractors in cortical neural networks with fixed synaptic weights. However, the variability in patterned behavior and the firing statistics of real neurons across the entire range of those behaviors across and within trials of working memory tasks are typical not reproduced. Here we examine the effect of dynamic synapses and network architectures with multiple cortical areas on the states and dynamics of working memory networks. The analysis indicates that the multiple pattern types exhibited by cells in working memory networks are inherent in networks with dynamic synapses, and that the variability and firing statistics in such networks with distributed architectures agree with that observed in the cortex

The relationship between occupational demands and well-being of performing artists: A systematic review

Background: Performing artists are exposed to a range of occupational demands from organisational, interpersonal and intrapersonal sources, which may impact their well-being. The aim of this systematic review was to evaluate and synthesise the literature where researchers have considered the relationship between occupational demands and well-being in performing artists. Methods: A mixed-methods systematic review was conducted including professional and student performing artists. Quantitative, qualitative and mixed-methods study designs were eligible for inclusion in the review. A total of 14 databases were searched from their inception through to October 2017, including MEDLINE, EMBASE and Scopus. Critical appraisal was conducted using the Mixed-Methods Appraisal Tool and results presented as a narrative synthesis. Results: A total of 20 studies were included in the review, comprising of quantitative (n=7), qualitative (n=9) and mixed-methods (n=4) study designs. Several frameworks of occupational stress and well-being were explored in relation to the results. Organisational, social and emotional demands were associated with lower well-being. Conversely, music-making, performance activities and social support were reported to be resources and were related to higher well-being. Conclusion: This systematic review highlights the need for researchers in this field to adopt methodologically robust study designs, which are informed by appropriate theoretical frameworks. The paucity of high quality and theoretically informed research in this area is a hindrance to the development of evidence-based interventions for this population

Neural Correlates of Feedback Processing in Visuo-Tactile Crossmodal Paired-Associate Learning

Previous studies have examined the neural correlates for crossmodal paired-associate (PA) memory and the temporal dynamics of its formation. However, the neural dynamics for feedback processing of crossmodal PA learning remain unclear. To examine this process, we recorded event-related scalp electrical potentials for PA learning of unimodal visual-visual pairs and crossmodal visual-tactile pairs when participants performed unimodal and crossmodal tasks. We examined event-related potentials (ERPs) after the onset of feedback in the tasks for three effects: feedback type (positive feedback vs. negative feedback), learning (as the learning progressed) and the task modality (crossmodal vs. unimodal). The results were as follows: (1) feedback type: the amplitude of P300 decreased with incorrect trials and the P400/N400 complex was only present in incorrect trials; (2) learning: progressive positive voltage shifts in frontal recording sites and negative voltage shifts in central and posterior recording sites were identified as learning proceeded; and (3) task modality: compared with the unimodal PA learning task, positive voltage shifts in frontal sites and negative voltage shifts in posterior sites were found in the crossmodal PA learning task. To sum up, these results shed light on cortical excitability related to feedback processing of crossmodal PA learning

Conformational Targeting of Fibrillar Polyglutamine Proteins in Live Cells Escalates Aggregation and Cytotoxicity

Misfolding- and aggregation-prone proteins underlying Parkinson's, Huntington's and Machado-Joseph diseases, namely alpha-synuclein, huntingtin, and ataxin-3 respectively, adopt numerous intracellular conformations during pathogenesis, including globular intermediates and insoluble amyloid-like fibrils. Such conformational diversity has complicated research into amyloid-associated intracellular dysfunction and neurodegeneration. To this end, recombinant single-chain Fv antibodies (scFvs) are compelling molecular tools that can be selected against specific protein conformations, and expressed inside cells as intrabodies, for investigative and therapeutic purposes.Using atomic force microscopy (AFM) and live-cell fluorescence microscopy, we report that a human scFv selected against the fibrillar form of alpha-synuclein targets isomorphic conformations of misfolded polyglutamine proteins. When expressed in the cytoplasm of striatal cells, this conformation-specific intrabody co-localizes with intracellular aggregates of misfolded ataxin-3 and a pathological fragment of huntingtin, and enhances the aggregation propensity of both disease-linked polyglutamine proteins. Using this intrabody as a tool for modulating the kinetics of amyloidogenesis, we show that escalating aggregate formation of a pathologic huntingtin fragment is not cytoprotective in striatal cells, but rather heightens oxidative stress and cell death as detected by flow cytometry. Instead, cellular protection is achieved by suppressing aggregation using a previously described intrabody that binds to the amyloidogenic N-terminus of huntingtin. Analogous cytotoxic results are observed following conformational targeting of normal or polyglutamine-expanded human ataxin-3, which partially aggregate through non-polyglutamine domains.These findings validate that the rate of aggregation modulates polyglutamine-mediated intracellular dysfunction, and caution that molecules designed to specifically hasten aggregation may be detrimental as therapies for polyglutamine disorders. Moreover, our findings introduce a novel antibody-based tool that, as a consequence of its general specificity for fibrillar conformations and its ability to function intracellularly, offers broad research potential for a variety of human amyloid diseases

Sequential Neural Processes in Abacus Mental Addition: An EEG and fMRI Case Study

Abacus experts are able to mentally calculate multi-digit numbers rapidly. Some behavioral and neuroimaging studies have suggested a visuospatial and visuomotor strategy during abacus mental calculation. However, no study up to now has attempted to dissociate temporally the visuospatial neural process from the visuomotor neural process during abacus mental calculation. In the present study, an abacus expert performed the mental addition tasks (8-digit and 4-digit addends presented in visual or auditory modes) swiftly and accurately. The 100% correct rates in this expert’s task performance were significantly higher than those of ordinary subjects performing 1-digit and 2-digit addition tasks. ERPs, EEG source localizations, and fMRI results taken together suggested visuospatial and visuomotor processes were sequentially arranged during the abacus mental addition with visual addends and could be dissociated from each other temporally. The visuospatial transformation of the numbers, in which the superior parietal lobule was most likely involved, might occur first (around 380 ms) after the onset of the stimuli. The visuomotor processing, in which the superior/middle frontal gyri were most likely involved, might occur later (around 440 ms). Meanwhile, fMRI results suggested that neural networks involved in the abacus mental addition with auditory stimuli were similar to those in the visual abacus mental addition. The most prominently activated brain areas in both conditions included the bilateral superior parietal lobules (BA 7) and bilateral middle frontal gyri (BA 6). These results suggest a supra-modal brain network in abacus mental addition, which may develop from normal mental calculation networks