A systematic review with meta-analysis of Yoga's contributions to neuropsychiatric aspects of aging.

Yoga is one of the most common Complementary and Alternative Medicines (CAM) for mind-body approaches to psychological and stress-related conditions in aging. Such wide usage demands the review and systematization of the scientific literature, searching for accumulated evidence of its effectiveness. We reviewed the literature to assess whether Yoga would offer significant improvements to neuropsychiatric aspects of the elderly: anxiety, depression, stress, memory and executive functions. METHODS: This systematic review with meta-analyses organized the results from all analyzed articles, comparing them between the experimental and either the control or waiting groups, calculating the effect size (Cohen-d) and the p-value of a two-tailed T-test. We presented the transformed metadata in forest graphs. RESULTS AND DISCUSSION: Given the heterogeneity of methods, results, and effect sizes of each study and due to the number of articles found, this meta-analysis indicates that it is not possible to state that Yoga reduces anxiety and stress in the elderly or improves cognition. However, this meta-analysis found significant results of Yoga in reducing depression with small to medium effect sizes. CONCLUSION: According to the currently available literature on Yoga and aspects of aging, we concluded that yoga was effective in most studies on reducing depression.

Directed functional and structural connectivity in a large-scale model for the mouse cortex.

Inferring the structural connectivity from electrophysiological measurements is a fundamental challenge in systems neuroscience. Directed functional connectivity measures, such as the generalized partial directed coherence (GPDC), provide estimates of the causal influence between areas. However, the relation between causality estimates and structural connectivity is still not clear. We analyzed this problem by evaluating the effectiveness of GPDC to estimate the connectivity of a ground-truth, data-constrained computational model of a large-scale network model of the mouse cortex. The model contains 19 cortical areas composed of spiking neurons, with areas connected by long-range projections with weights obtained from a tract-tracing cortical connectome. We show that GPDC values provide a reasonable estimate of structural connectivity, with an average Pearson correlation over simulations of 0.74. Moreover, even in a typical electrophysiological recording scenario containing five areas, the mean correlation was above 0.6. These results suggest that it may be possible to empirically estimate structural connectivity from functional connectivity even when detailed whole-brain recordings are not achievable.

Temporal regularity and stimulus control in multiple fixed interval schedules.

In multiple fixed interval schedules of reinforcement, different time intervals are signaled by different environmental stimuli which acquire control over behavior. Previous work has shown that temporal performance is controlled not only by external stimuli but also by temporal aspects of the task, depending on the order in which the different intervals are trained - intermixed across trials or in blocks of several trials. The aim of this study was to further describe the training conditions under which the stimuli acquire control over temporal performance. We manipulated the number of consecutive trials of each fixed interval (FI) per training block (Experiment I) and the number of FIs trained (Experiment II). The results suggest that when trained in blocks of several consecutive trials of the same FI, temporal performance is controlled by temporal regularities across trials and not by the visual stimuli that signal the FIs. One possible account for those data is that the temporal cues overshadow the visual stimuli for the control of temporal performance. Similar results have also been observed with humans, which suggest that temporal regularity overcomes the stimuli in the control of behavior in temporal tasks across species.

Evaluation of connectivity estimates using spiking neuronal network models.

The flow of information between different regions of the cortex is fundamental for brain function. Researchers use causality detection techniques, such as Granger causality, to infer connectivity among brain areas from time series. Generalized partial directed coherence (GPDC) is a frequency domain linear method based on vector autoregressive model, which has been applied in electroencephalography, local field potential, and blood oxygenation level-dependent signals. Despite its widespread usage, previous attempts to validate GPDC use oversimplified simulated data, which do not reflect the nonlinearities and network couplings present in biological signals. In this work, we evaluated the GPDC performance when applied to simulated LFP signals, i.e., generated from networks of spiking neuronal models. We created three models, each containing five interacting networks, and evaluated whether the GPDC method could accurately detect network couplings. When using a stronger coupling, we showed that GPDC correctly detects all existing connections from simulated LFP signals in the three models, without false positives. Varying the coupling strength between networks, by changing the number of connections or synaptic strengths, and adding noise in the times series, altered the receiver operating characteristic (ROC) curve, ranging from perfect to chance level retrieval. We also showed that GPDC values correlated with coupling strength, indicating that GPDC values can provide useful information regarding coupling strength. These results reinforce that GPDC can be used to detect causality relationships over neural signals.

Inactivation of the Medial-Prefrontal Cortex Impairs Interval Timing Precision, but Not Timing Accuracy or Scalar Timing in a Peak-Interval Procedure in Rats.

Motor sequence learning, planning and execution of goal-directed behaviors, and decision making rely on accurate time estimation and production of durations in the seconds-to-minutes range. The pathways involved in planning and execution of goal-directed behaviors include cortico-striato-thalamo-cortical circuitry modulated by dopaminergic inputs. A critical feature of interval timing is its scalar property, by which the precision of timing is proportional to the timed duration. We examined the role of medial prefrontal cortex (mPFC) in timing by evaluating the effect of its reversible inactivation on timing accuracy, timing precision and scalar timing. Rats were trained to time two durations in a peak-interval (PI) procedure. Reversible mPFC inactivation using GABA agonist muscimol resulted in decreased timing precision, with no effect on timing accuracy and scalar timing. These results are partly at odds with studies suggesting that ramping prefrontal activity is crucial to timing but closely match simulations with the Striatal Beat Frequency (SBF) model proposing that timing is coded by the coincidental activation of striatal neurons by cortical inputs. Computer simulations indicate that in SBF, gradual inactivation of cortical inputs results in a gradual decrease in timing precision with preservation of timing accuracy and scalar timing. Further studies are needed to differentiate between timing models based on coincidence detection and timing models based on ramping mPFC activity, and clarify whether mPFC is specifically involved in timing, or more generally involved in attention, working memory, or response selection/inhibition.

Heteroassociative storage of hippocampal pattern sequences in the CA3 subregion.

BACKGROUND: Recent research suggests that the CA3 subregion of the hippocampus has properties of both autoassociative network, due to its ability to complete partial cues, tolerate noise, and store associations between memories, and heteroassociative one, due to its ability to store and retrieve sequences of patterns. Although there are several computational models of the CA3 as an autoassociative network, more detailed evaluations of its heteroassociative properties are missing. METHODS: We developed a model of the CA3 subregion containing 10,000 integrate-and-fire neurons with both recurrent excitatory and inhibitory connections, and which exhibits coupled oscillations in the gamma and theta ranges. We stored thousands of pattern sequences using a heteroassociative learning rule with competitive synaptic scaling. RESULTS: We showed that a purely heteroassociative network model can (i) retrieve pattern sequences from partial cues with external noise and incomplete connectivity, (ii) achieve homeostasis regarding the number of connections per neuron when many patterns are stored when using synaptic scaling, (iii) continuously update the set of retrievable patterns, guaranteeing that the last stored patterns can be retrieved and older ones can be forgotten. DISCUSSION: Heteroassociative networks with synaptic scaling rules seem sufficient to achieve many desirable features regarding connectivity homeostasis, pattern sequence retrieval, noise tolerance and updating of the set of retrievable patterns.

Dynamic representation of time in brain states.

The ability to process time on the scale of milliseconds and seconds is essential for behaviour. A growing number of studies have started to focus on brain dynamics as a mechanism for temporal encoding. Although there is growing evidence in favour of this view from computational and in vitro studies, there is still a lack of results from experiments in humans. We show that high-dimensional brain states revealed by multivariate pattern analysis of human EEG are correlated to temporal judgements. First, we show that, as participants estimate temporal intervals, the spatiotemporal dynamics of their brain activity are consistent across trials. Second, we present evidence that these dynamics exhibit properties of temporal perception, such as scale invariance. Lastly, we show that it is possible to predict temporal judgements based on brain states. These results show how scalp recordings can reveal the spatiotemporal dynamics of human brain activity related to temporal processing.

Artificial synaptic modification reveals a dynamical invariant in the pyloric CPG.

The sequential firing of neurons in central pattern generators (CPGs) is generally thought to be a result of an interaction between intrinsic cellular and synaptic properties of the component neurons. Due to experimental limitations, it is usually difficult to address the role of each of these properties separately. We have done so by using the crustacean stomatogastric CPG and the dynamic clamp technique to measure how the network responds to the selective modification of an individual important synapse. Our results show that the burst periods and the phase lags between the constrictor (LP) and dilator (PD) neurons across preparations showed significant variability during equivalent experimental manipulations. Despite this variability, the ratio between the change in the burst period and the change in the phase lag between the same neurons was tightly preserved in all preparations, revealing a dynamical invariant in the system. This dynamical invariant was preserved despite the individual variability in the period and phase lag measurements, suggesting a tightly regulated constraint between the parameters of the network.

Whole cell stochastic model reproduces the irregularities found in the membrane potential of bursting neurons.

Irregular intrinsic behavior of neurons seems ubiquitous in the nervous system. Even in circuits specialized to provide periodic and reliable patterns to control the repetitive activity of muscles, such as the pyloric central pattern generator (CPG) of the crustacean stomatogastric ganglion (STG), many bursting motor neurons present irregular activity when deprived from synaptic inputs. Moreover, many authors attribute to these irregularities the role of providing flexibility and adaptation capabilities to oscillatory neural networks such as CPGs. These irregular behaviors, related to nonlinear and chaotic properties of the cells, pose serious challenges to developing deterministic Hodgkin-Huxley-type (HH-type) conductance models. Only a few deterministic HH-type models based on experimental conductance values were able to show such nonlinear properties, but most of these models are based on slow oscillatory dynamics of the cytosolic calcium concentration that were never found experimentally in STG neurons. Based on an up-to-date single-compartment deterministic HH-type model of a STG neuron, we developed a stochastic HH-type model based on the microscopic Markovian states that an ion channel can achieve. We used tools from nonlinear analysis to show that the stochastic model is able to express the same kind of irregularities, sensitivity to initial conditions, and low dimensional dynamics found in the neurons isolated from the STG. Without including any nonrealistic dynamics in our whole cell stochastic model, we show that the nontrivial dynamics of the membrane potential naturally emerge from the interplay between the microscopic probabilistic character of the ion channels and the nonlinear interactions among these elements. Moreover, the experimental irregular behavior is reproduced by the stochastic model for the same parameters for which the membrane potential of the original deterministic model exhibits periodic oscillations.